The phylogenetic relationships among the Nepomorpha (Hemiptera: Heteroptera) were analyzed based on nuclear protein coding genes-partial sequences of four Hox genes: abd-A, Dfd, Ubx and pb. Fifteen taxa, of which ...The phylogenetic relationships among the Nepomorpha (Hemiptera: Heteroptera) were analyzed based on nuclear protein coding genes-partial sequences of four Hox genes: abd-A, Dfd, Ubx and pb. Fifteen taxa, of which eleven were ingroups representing ten of the eleven families, were selected to produce a phylogenetic inference of nepomorphan superfamilial or familial relationships via parsimony and Bayesian techniques. Our results supported the monophylies of Nepomorpha, Naucoroidea (Aphelocheiridae + Naucoridae), Nepoidea (Belostomatidae + Nepidae), Ochteroidea (Ochteridae + Gelastocoridae) and Pieoidea (Pleidae + Helotrephidae); the most basal lineage of Ochteroidea; Notonectoidea contained Notonectidae only and formed a new sister relationship with (Pleoidea + Naucoroidea); and the sister relationship of (Nepoidea + Corixoidea). The Hox genes are suitable molecular markers to resolve phylogenetic relationships at superfamily or family levels in Heteroptera.展开更多
Homeobox genes, including HOX and non-HOX genes, have been identified to be expressed aberrantly in solid tumors. In gastrointestinal(GI) cancers, most studies have focused on the function of non-HOX genes including c...Homeobox genes, including HOX and non-HOX genes, have been identified to be expressed aberrantly in solid tumors. In gastrointestinal(GI) cancers, most studies have focused on the function of non-HOX genes including caudal-related homeobox transcription factor 1(CDX1) and CDX2. CDX2 is a crucial factor in the development of pre-cancerous lesions such as Barrett's esophagus or intestinal metaplasia in the stomach, and its tumor suppressive role has been investigated in colorectal cancers. Recently, several HOX genes were reported to have specific roles in GI cancers; for example, HOXA13 in esophageal squamous cell cancer and HOXB7 in stomach and colorectal cancers. HOXD10 is upregulated in colorectal cancer while it is silenced epigenetically in gastric cancer. Thus, it is essential to examine the differential expression pattern of various homeobox genes in specific tumor types or cell lineages, and understand their underlying mechanisms. In this review, we summarize the available research on homeobox genes and present their potential value for the prediction of prognosis in GI cancers.展开更多
Hox genes are an evolutionary highly conserved gene family. They determine the anterior-posterior body axis in bilateral organisms and influence the developmental fate of cells. Embryonic stem cells are usually devoid...Hox genes are an evolutionary highly conserved gene family. They determine the anterior-posterior body axis in bilateral organisms and influence the developmental fate of cells. Embryonic stem cells are usually devoidof any Hox gene expression, but these transcription factors are activated in varying spatial and temporal patterns defining the development of various body regions. In the adult body, Hox genes are among others responsible for driving the differentiation of tissue stem cells towards their respective lineages in order to repair and maintain the correct function of tissues and organs. Due to their involvement in the embryonic and adult body, they have been suggested to be useable for improving stem cell differentiations in vitro and in vivo. In many studies Hox genes have been found as driving factors in stem cell differentiation towards adipogenesis, in lineages involved in bone and joint formation, mainly chondrogenesis and osteogenesis, in cardiovascular lineages including endothelial and smooth muscle cell differentiations, and in neurogenesis. As life expectancy is rising, the demand for tissue reconstruction continues to increase. Stem cells have become an increasingly popular choice for creating therapies in regenerative medicine due to their self-renewal and differentiation potential. Especially mesenchymal stem cells are used more and more frequently due to their easy handling and accessibility, combined with a low tumorgenicity and little ethical concerns. This review therefore intends to summarize to date known correlations between natural Hox gene expression patterns in body tissues and during the differentiation of various stem cells towards their respective lineages with a major focus on mesenchymal stem cell differentiations. This overview shall help to understand the complex interactions of Hox genes and differentiation processes all over the body as well as in vitro for further improvement of stem cell treatments in future regenerative medicine approaches.展开更多
The proper development of uterus to a state of receptivity and the attainment of implantation competency for blastocyst are 2 indispensable aspects for implantation,which is considered to be a critical event for succe...The proper development of uterus to a state of receptivity and the attainment of implantation competency for blastocyst are 2 indispensable aspects for implantation,which is considered to be a critical event for successful pregnancy. Like many developmental processes, a large number of transcription factors, such as homeobox genes, have been shown to orchestrate this complicated but highly organized physiological process during implantation. In this review, we focus on progress in studies of the role of homeobox genes, especially the Hox and Msx gene families, during implantation, together with subsequent development of post-implantation uterus and related reproductive defects in both mouse models and humans, that have led to better understanding of how implantation is precisely regulated and provide new insights into infertility.展开更多
AIM:To identify methylation profile and novel tumor marker of extrahepatic cholangiocarcinoma(CCA)with high throughout microarray.METHODS:Differential methylation profile was compared between normal bile duct epitheli...AIM:To identify methylation profile and novel tumor marker of extrahepatic cholangiocarcinoma(CCA)with high throughout microarray.METHODS:Differential methylation profile was compared between normal bile duct epithelial cell lines and CCA cell lines by methyl-DNA immunoprecipitation (MeDIP)microarray.Bisulfite-polymerase chain reaction (BSP)was performed to identify the methylated allels of target genes.Expression of target genes was investigated before and after the treatment with DNA demethylating agent.Expression of candidate genes was also evaluated by immunofluorescence in 30 specimens of CCA tissues and 9 normal bile duct tissues.RESULTS:Methylation profile of CCA was identified with MeDIP microarray in the respects of different gene functions and signaling pathways.Interestingly,97 genes with hypermethylated CpG islands in the promoter region were homeobox genes.The top 5 hypermethylated homeobox genes validated by BSP were HOXA2(94.29%),HOXA5(95.38%),HOXA11 (91.67%),HOXB4(90.56%)and HOXD13(94.38%).Expression of these genes was reactivated with 5’-aza2’-deoxycytidine.Significant expression differences were found between normal bile duct and extrahepatic CCA tissues(66.67%-100%vs 3.33%-10%).CONCLUSION:HOXA2,HOXA5,HOXA11,HOXB4 and HOXD13 may work as differential epigenetic biomarkers between malignant and benign biliary tissues.展开更多
Homeobox genes have been discovered in many species. These genes are known to play a major role in specifying regional identity along the anterior-posterior axis of animals from a wide range of phyla.The products of t...Homeobox genes have been discovered in many species. These genes are known to play a major role in specifying regional identity along the anterior-posterior axis of animals from a wide range of phyla.The products of the homeotic genes are a set of evolutionarily conserved transcription factors that control elaborate developmental processes and specify cell fates in metazoans. Crustacean, presenting a variety of body plans not encountered in any other class or phylum of the Metazoa, has been shown to possess a single set of homologous Hox genes like insect. The ancestral crustacean Hox gene complex comprised ten genes: eight homologous to the hometic Hox genes and two related to nonhomeotic genes presented within the insect Hox complexes. The crustacean in particular exhibits an abundant diversity segment specialization and tagmosis. This morphological diversity relates to the Hox genes. In crustacean body plan, different Hox genes control different segments and tagmosis.展开更多
To study the effects of phenylacetate (PA) on cell proliferation and homeobox (HOX) genes expression in the colorectal carcinoma HCT-8 cell line, HCT-8 cells were grown in the presence or absence of PA. The cellul...To study the effects of phenylacetate (PA) on cell proliferation and homeobox (HOX) genes expression in the colorectal carcinoma HCT-8 cell line, HCT-8 cells were grown in the presence or absence of PA. The cellular proliferation inhibition was evaluated by the MTT assay. Twenty-two HOX genes were divided into three groups ( P1, P2, P3) according to their primer sequences, and the samples of cells were analyzed for the HOX genes' mRNA expression by means of the semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The level of the HOX genes' expression was expressed as the ratio expression rate of HOX gene to the β-actin. HCT-8 cells were treated with 1.0-5.0 mmol/L PA for 24-72 h. With the increase of the PA concentration or the prolongation of the treating time, the cell proliferation is inhibited in a dose- and time-dependent manner. The P1 group mRNA* expression(0. 5781 ±0. 0836) is significantly lower than that of the untreated group (0. 7701 ± 0. 0883 ) in HCT-8 cells (p 〈 0. 001 ). Both the mRNA expressions of groups P2 (0. 3941 ± 0. 0819) and P3 (0. 5601 ± 0. 0736) in the PA treated group are significantly higher than those of the untreated groups P2(0. 1221±0. 0782) and P3 (0. 1806 ± 0. 0811 ) in HCT-8 cells(p 〈 0. 001). PA could effectively inhibit cell proliferation by regulating the HOX genes expression and the mechanisms of the PA action are correlated with the transcription process in HCT-8 cells.展开更多
The three-dimensional(3D) organization of the eukaryotic genome is critical for its proper function. Evidence suggests that extensive chromatin loops form the building blocks of the genomic architecture, separating ge...The three-dimensional(3D) organization of the eukaryotic genome is critical for its proper function. Evidence suggests that extensive chromatin loops form the building blocks of the genomic architecture, separating genes and gene clusters into distinct functional domains. These loops are anchored in part by a special type of DNA elements called chromatin boundary elements(CBEs). CBEs were originally found to insulate neighboring genes by blocking influences of transcriptional enhancers or the spread of silent chromatin. However, recent results show that chromatin loops can also play a positive role in gene regulation by looping out intervening DNA and "delivering" remote enhancers to gene promoters. In addition, studies from human and model organisms indicate that the configuration of chromatin loops, many of which are tethered by CBEs, is dynamically regulated during cell differentiation. In particular, a recent work by Li et al has shown that the SF1 boundary, located in the Drosophila Hox cluster, regulates local genes by tethering different subsets of chromatin loops: One subset enclose a neighboring gene ftz, limiting its access by the surrounding Scr enhancers and restrict the spread of repressive histones during early embryogenesis; and the other loops subdivide the Scr regulatory region into independent domains of enhancer accessibility. The enhancer-blocking activity of these CBE elements varies greatly in strength and tissue distribution. Further, tandem pairing of SF1 and SF2 facilitate the bypass of distal enhancers in transgenic flies, providing a mechanism for endogenous enhancers to circumvent genomic interruptions resulting from chromosomal rearrangement. This study demonstrates how a network of chromatin boundaries, centrally organized by SF1, can remodel the 3D genome to facilitate gene regulation during development.展开更多
BACKGROUND The distal-less homeobox(DLX)gene family plays an important role in the development of several tumors.However,the expression pattern,prognostic and diagnostic value,possible regulatory mechanisms,and the re...BACKGROUND The distal-less homeobox(DLX)gene family plays an important role in the development of several tumors.However,the expression pattern,prognostic and diagnostic value,possible regulatory mechanisms,and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported.AIM We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer.METHODS Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases.Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue.cBioPortal was used to analyze DLX gene family variants.R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map.The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family.The pROC package was used to analyze the diagnostic value of the DLX gene family.R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes.The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration.The ggplot2,the survminer package,and the clusterProfiler package were used for visualization.RESULTS DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients.The expression of DLX genes were associated with M stage,pathologic stage,primary therapy outcome,residual tumor,lymphatic invasion,T stage,N stage,age,perineural invasion,and history of colon polyps.DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis.DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways,including the Hippo signaling pathway,the Wnt signaling pathway,several signaling pathways regulating the pluripotency of stem cells,and Staphylococcus aureus infection.CONCLUSION The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.展开更多
Archetypes of histone modifications associated with diverse chromosomal states that regulate access to DNA are leading the hypothesis of the histone code(or epigenetic code). However, it is still not evident how these...Archetypes of histone modifications associated with diverse chromosomal states that regulate access to DNA are leading the hypothesis of the histone code(or epigenetic code). However, it is still not evident how these post-translational modifications of histone tails lead to changes in chromatin structure. Histone modifications are able to activate and/or inactivate several genes and can be transmitted to next generation cells due to an epigenetic memory. The challenging issue is to identify or "decrypt" the code used to transmit these modifications to descent cells. Here, an attempt is made to describe how histone modifications operate as part of histone code that stipulates patterns of gene expression. This papers emphasizes particularly on the correlation between histone modifications and patterns of Hox gene expression in Caenorhabditis elegans. This work serves as an example to illustrate the power of the epigenetic machinery and its use in drug design and discovery.展开更多
Study Design: Between January 2003 and June 2009, we collected fresh tumor and extracted high-quality RNA from the omental/peritoneal metastases of 47 patients with stage IIB-IV ovarian cancer. Clinical data were abst...Study Design: Between January 2003 and June 2009, we collected fresh tumor and extracted high-quality RNA from the omental/peritoneal metastases of 47 patients with stage IIB-IV ovarian cancer. Clinical data were abstracted from the patients’ medical records. Expression of Six1 level by quantitative RT-PCR was compared with preoperative factors and intraoperative findings using the χ2 test and the Fisher exact test. The effect of Six1 elevation on survival was assessed with the Kaplan/Meier method. Results: The mean age of patients enrolled was 60 (range 33 - 84). The histological subtypes were 77% serous (36/47), 11% endometrioid (5/47), 4% mucinous (2/47), and 4% clear cell (2/47). Eighty-one percent were optimally cytoreduced. Median Six1 expression for the samples was 114 fg/ng 18S rRNA and Six1 overexpression, defined as >300 fg/ng 18S rRNA, was observed in 19% of tumors. Six1 expression above sample median was associated with peritoneal disease (p = 0.049) and inability to optimally cytoreduce (p = 0.02). Six1 overexpression was associated with worsened survival in the high grade serous subgroup (43 months versus 71 months, p = 0.039 Log Rank test). Conclusions: Elevated levels of Six1 predict peritoneal disease and larger residual tumor after maximal cytoreductive effort. Prospective prediction of surgical cytoreduction using a combination of Six1 expression, included with other factors, is currently being evaluated.展开更多
Most of the plant homeodomain-containing proteins play important roles in regulating cell differentiation and organ development,and Arabidopsis GLABRA2(GL2),a member of the class IV homeodomain-Leucine zipper(HD-ZIP) ...Most of the plant homeodomain-containing proteins play important roles in regulating cell differentiation and organ development,and Arabidopsis GLABRA2(GL2),a member of the class IV homeodomain-Leucine zipper(HD-ZIP) proteins,is a trichome and non-root hair cell regulator.We展开更多
基金supported by the Natural Science Foundation of China(Nos.30725005,31071959,J0930005)supported by the Ministry of Education of China(No.20100031110026)
文摘The phylogenetic relationships among the Nepomorpha (Hemiptera: Heteroptera) were analyzed based on nuclear protein coding genes-partial sequences of four Hox genes: abd-A, Dfd, Ubx and pb. Fifteen taxa, of which eleven were ingroups representing ten of the eleven families, were selected to produce a phylogenetic inference of nepomorphan superfamilial or familial relationships via parsimony and Bayesian techniques. Our results supported the monophylies of Nepomorpha, Naucoroidea (Aphelocheiridae + Naucoridae), Nepoidea (Belostomatidae + Nepidae), Ochteroidea (Ochteridae + Gelastocoridae) and Pieoidea (Pleidae + Helotrephidae); the most basal lineage of Ochteroidea; Notonectoidea contained Notonectidae only and formed a new sister relationship with (Pleoidea + Naucoroidea); and the sister relationship of (Nepoidea + Corixoidea). The Hox genes are suitable molecular markers to resolve phylogenetic relationships at superfamily or family levels in Heteroptera.
基金Supported by the Korean College of Helicobacter and Upper Gastrointestinal Research Foundation Granta Korea University Grant,No.K1512661
文摘Homeobox genes, including HOX and non-HOX genes, have been identified to be expressed aberrantly in solid tumors. In gastrointestinal(GI) cancers, most studies have focused on the function of non-HOX genes including caudal-related homeobox transcription factor 1(CDX1) and CDX2. CDX2 is a crucial factor in the development of pre-cancerous lesions such as Barrett's esophagus or intestinal metaplasia in the stomach, and its tumor suppressive role has been investigated in colorectal cancers. Recently, several HOX genes were reported to have specific roles in GI cancers; for example, HOXA13 in esophageal squamous cell cancer and HOXB7 in stomach and colorectal cancers. HOXD10 is upregulated in colorectal cancer while it is silenced epigenetically in gastric cancer. Thus, it is essential to examine the differential expression pattern of various homeobox genes in specific tumor types or cell lineages, and understand their underlying mechanisms. In this review, we summarize the available research on homeobox genes and present their potential value for the prediction of prognosis in GI cancers.
基金BMBF,Adi Pa D,1720X06,BMBF,FHprof Unt,FKZ:03FH012PB2FH-Extra,"Europischer Fonds für regionale Entwicklung","Europa-Investition in unsere Zukunft",FKZ:z1112fh012EFRE co-financed NRW Ziel 2:"Regionale Wettbewerbsfhigkeit und Beschftigung",DAAD,PPP Vigoni,FKZ:314-vigoni-dr and FKZ:54669218 for Edda Tobiasch
文摘Hox genes are an evolutionary highly conserved gene family. They determine the anterior-posterior body axis in bilateral organisms and influence the developmental fate of cells. Embryonic stem cells are usually devoidof any Hox gene expression, but these transcription factors are activated in varying spatial and temporal patterns defining the development of various body regions. In the adult body, Hox genes are among others responsible for driving the differentiation of tissue stem cells towards their respective lineages in order to repair and maintain the correct function of tissues and organs. Due to their involvement in the embryonic and adult body, they have been suggested to be useable for improving stem cell differentiations in vitro and in vivo. In many studies Hox genes have been found as driving factors in stem cell differentiation towards adipogenesis, in lineages involved in bone and joint formation, mainly chondrogenesis and osteogenesis, in cardiovascular lineages including endothelial and smooth muscle cell differentiations, and in neurogenesis. As life expectancy is rising, the demand for tissue reconstruction continues to increase. Stem cells have become an increasingly popular choice for creating therapies in regenerative medicine due to their self-renewal and differentiation potential. Especially mesenchymal stem cells are used more and more frequently due to their easy handling and accessibility, combined with a low tumorgenicity and little ethical concerns. This review therefore intends to summarize to date known correlations between natural Hox gene expression patterns in body tissues and during the differentiation of various stem cells towards their respective lineages with a major focus on mesenchymal stem cell differentiations. This overview shall help to understand the complex interactions of Hox genes and differentiation processes all over the body as well as in vitro for further improvement of stem cell treatments in future regenerative medicine approaches.
基金National Natural Science Foundation of China,Grant/Award Number:81330017,81490744National Key R&D Program of China,Grant/Award Number:2017YFC1001402
文摘The proper development of uterus to a state of receptivity and the attainment of implantation competency for blastocyst are 2 indispensable aspects for implantation,which is considered to be a critical event for successful pregnancy. Like many developmental processes, a large number of transcription factors, such as homeobox genes, have been shown to orchestrate this complicated but highly organized physiological process during implantation. In this review, we focus on progress in studies of the role of homeobox genes, especially the Hox and Msx gene families, during implantation, together with subsequent development of post-implantation uterus and related reproductive defects in both mouse models and humans, that have led to better understanding of how implantation is precisely regulated and provide new insights into infertility.
基金Supported by The grant for"Development of Novel Nano-Drug Delivery System Loaded with Traditional Chinese Anticancer Medicine for the Targeted Therapy of Malignant Tumors"issued by the Chinese Ministry of Science and Technology,Grant No. 2010DFA31870
文摘AIM:To identify methylation profile and novel tumor marker of extrahepatic cholangiocarcinoma(CCA)with high throughout microarray.METHODS:Differential methylation profile was compared between normal bile duct epithelial cell lines and CCA cell lines by methyl-DNA immunoprecipitation (MeDIP)microarray.Bisulfite-polymerase chain reaction (BSP)was performed to identify the methylated allels of target genes.Expression of target genes was investigated before and after the treatment with DNA demethylating agent.Expression of candidate genes was also evaluated by immunofluorescence in 30 specimens of CCA tissues and 9 normal bile duct tissues.RESULTS:Methylation profile of CCA was identified with MeDIP microarray in the respects of different gene functions and signaling pathways.Interestingly,97 genes with hypermethylated CpG islands in the promoter region were homeobox genes.The top 5 hypermethylated homeobox genes validated by BSP were HOXA2(94.29%),HOXA5(95.38%),HOXA11 (91.67%),HOXB4(90.56%)and HOXD13(94.38%).Expression of these genes was reactivated with 5’-aza2’-deoxycytidine.Significant expression differences were found between normal bile duct and extrahepatic CCA tissues(66.67%-100%vs 3.33%-10%).CONCLUSION:HOXA2,HOXA5,HOXA11,HOXB4 and HOXD13 may work as differential epigenetic biomarkers between malignant and benign biliary tissues.
文摘Homeobox genes have been discovered in many species. These genes are known to play a major role in specifying regional identity along the anterior-posterior axis of animals from a wide range of phyla.The products of the homeotic genes are a set of evolutionarily conserved transcription factors that control elaborate developmental processes and specify cell fates in metazoans. Crustacean, presenting a variety of body plans not encountered in any other class or phylum of the Metazoa, has been shown to possess a single set of homologous Hox genes like insect. The ancestral crustacean Hox gene complex comprised ten genes: eight homologous to the hometic Hox genes and two related to nonhomeotic genes presented within the insect Hox complexes. The crustacean in particular exhibits an abundant diversity segment specialization and tagmosis. This morphological diversity relates to the Hox genes. In crustacean body plan, different Hox genes control different segments and tagmosis.
文摘To study the effects of phenylacetate (PA) on cell proliferation and homeobox (HOX) genes expression in the colorectal carcinoma HCT-8 cell line, HCT-8 cells were grown in the presence or absence of PA. The cellular proliferation inhibition was evaluated by the MTT assay. Twenty-two HOX genes were divided into three groups ( P1, P2, P3) according to their primer sequences, and the samples of cells were analyzed for the HOX genes' mRNA expression by means of the semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The level of the HOX genes' expression was expressed as the ratio expression rate of HOX gene to the β-actin. HCT-8 cells were treated with 1.0-5.0 mmol/L PA for 24-72 h. With the increase of the PA concentration or the prolongation of the treating time, the cell proliferation is inhibited in a dose- and time-dependent manner. The P1 group mRNA* expression(0. 5781 ±0. 0836) is significantly lower than that of the untreated group (0. 7701 ± 0. 0883 ) in HCT-8 cells (p 〈 0. 001 ). Both the mRNA expressions of groups P2 (0. 3941 ± 0. 0819) and P3 (0. 5601 ± 0. 0736) in the PA treated group are significantly higher than those of the untreated groups P2(0. 1221±0. 0782) and P3 (0. 1806 ± 0. 0811 ) in HCT-8 cells(p 〈 0. 001). PA could effectively inhibit cell proliferation by regulating the HOX genes expression and the mechanisms of the PA action are correlated with the transcription process in HCT-8 cells.
文摘The three-dimensional(3D) organization of the eukaryotic genome is critical for its proper function. Evidence suggests that extensive chromatin loops form the building blocks of the genomic architecture, separating genes and gene clusters into distinct functional domains. These loops are anchored in part by a special type of DNA elements called chromatin boundary elements(CBEs). CBEs were originally found to insulate neighboring genes by blocking influences of transcriptional enhancers or the spread of silent chromatin. However, recent results show that chromatin loops can also play a positive role in gene regulation by looping out intervening DNA and "delivering" remote enhancers to gene promoters. In addition, studies from human and model organisms indicate that the configuration of chromatin loops, many of which are tethered by CBEs, is dynamically regulated during cell differentiation. In particular, a recent work by Li et al has shown that the SF1 boundary, located in the Drosophila Hox cluster, regulates local genes by tethering different subsets of chromatin loops: One subset enclose a neighboring gene ftz, limiting its access by the surrounding Scr enhancers and restrict the spread of repressive histones during early embryogenesis; and the other loops subdivide the Scr regulatory region into independent domains of enhancer accessibility. The enhancer-blocking activity of these CBE elements varies greatly in strength and tissue distribution. Further, tandem pairing of SF1 and SF2 facilitate the bypass of distal enhancers in transgenic flies, providing a mechanism for endogenous enhancers to circumvent genomic interruptions resulting from chromosomal rearrangement. This study demonstrates how a network of chromatin boundaries, centrally organized by SF1, can remodel the 3D genome to facilitate gene regulation during development.
文摘BACKGROUND The distal-less homeobox(DLX)gene family plays an important role in the development of several tumors.However,the expression pattern,prognostic and diagnostic value,possible regulatory mechanisms,and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported.AIM We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer.METHODS Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases.Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue.cBioPortal was used to analyze DLX gene family variants.R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map.The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family.The pROC package was used to analyze the diagnostic value of the DLX gene family.R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes.The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration.The ggplot2,the survminer package,and the clusterProfiler package were used for visualization.RESULTS DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients.The expression of DLX genes were associated with M stage,pathologic stage,primary therapy outcome,residual tumor,lymphatic invasion,T stage,N stage,age,perineural invasion,and history of colon polyps.DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis.DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways,including the Hippo signaling pathway,the Wnt signaling pathway,several signaling pathways regulating the pluripotency of stem cells,and Staphylococcus aureus infection.CONCLUSION The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.
文摘Archetypes of histone modifications associated with diverse chromosomal states that regulate access to DNA are leading the hypothesis of the histone code(or epigenetic code). However, it is still not evident how these post-translational modifications of histone tails lead to changes in chromatin structure. Histone modifications are able to activate and/or inactivate several genes and can be transmitted to next generation cells due to an epigenetic memory. The challenging issue is to identify or "decrypt" the code used to transmit these modifications to descent cells. Here, an attempt is made to describe how histone modifications operate as part of histone code that stipulates patterns of gene expression. This papers emphasizes particularly on the correlation between histone modifications and patterns of Hox gene expression in Caenorhabditis elegans. This work serves as an example to illustrate the power of the epigenetic machinery and its use in drug design and discovery.
文摘Study Design: Between January 2003 and June 2009, we collected fresh tumor and extracted high-quality RNA from the omental/peritoneal metastases of 47 patients with stage IIB-IV ovarian cancer. Clinical data were abstracted from the patients’ medical records. Expression of Six1 level by quantitative RT-PCR was compared with preoperative factors and intraoperative findings using the χ2 test and the Fisher exact test. The effect of Six1 elevation on survival was assessed with the Kaplan/Meier method. Results: The mean age of patients enrolled was 60 (range 33 - 84). The histological subtypes were 77% serous (36/47), 11% endometrioid (5/47), 4% mucinous (2/47), and 4% clear cell (2/47). Eighty-one percent were optimally cytoreduced. Median Six1 expression for the samples was 114 fg/ng 18S rRNA and Six1 overexpression, defined as >300 fg/ng 18S rRNA, was observed in 19% of tumors. Six1 expression above sample median was associated with peritoneal disease (p = 0.049) and inability to optimally cytoreduce (p = 0.02). Six1 overexpression was associated with worsened survival in the high grade serous subgroup (43 months versus 71 months, p = 0.039 Log Rank test). Conclusions: Elevated levels of Six1 predict peritoneal disease and larger residual tumor after maximal cytoreductive effort. Prospective prediction of surgical cytoreduction using a combination of Six1 expression, included with other factors, is currently being evaluated.
文摘Most of the plant homeodomain-containing proteins play important roles in regulating cell differentiation and organ development,and Arabidopsis GLABRA2(GL2),a member of the class IV homeodomain-Leucine zipper(HD-ZIP) proteins,is a trichome and non-root hair cell regulator.We