Chondrocyte differentiation is a critical process for endochondral ossification,which is responsible for long bone development and fracture repair.Considerable progress has been made in understanding the transcription...Chondrocyte differentiation is a critical process for endochondral ossification,which is responsible for long bone development and fracture repair.Considerable progress has been made in understanding the transcriptional control of chondrocyte differentiation;however,epigenetic regulation of chondrocyte differentiation remains to be further studied.NSD1 is a H3K36(histone H3 at lysine 36)methyltransferase.Here,we showed that mice with Nsd1 deficiency in Prx1+mesenchymal progenitors but not in Col2+chondrocytes showed impaired skeletal growth and fracture healing accompanied by decreased chondrogenic differentiation.Via combined RNA sequencing(RNA-seq)and chromatin immunoprecipitation sequencing(ChIP-seq)analysis,we identified sex determining region Y box 9(Sox9),the key transcription factor of chondrogenic differentiation,as a functional target gene of NSD1.Mechanistically,NSD1 regulates Sox9 expression by modulating H3K36me1 and H3K36me2 levels in the Sox9 promoter region,constituting a novel epigenetic regulatory mechanism of chondrogenesis.Moreover,we found that NSD1 can directly activate the expression of hypoxia-inducible factor 1α(HIF1α),which plays a vital role in chondrogenic differentiation through its regulation of Sox9 expression.Collectively,the results of our study reveal crucial roles of NSD1 in regulating chondrogenic differentiation,skeletal growth,and fracture repair and expand our understanding of the function of epigenetic regulation in chondrogenesis and skeletal biology.展开更多
Previous studies demonstrated that adult murine prostate basal and luminal cells are independently self-sustained, but prostate basal cells possess the potential to differentiate into multiple lineages upon induction ...Previous studies demonstrated that adult murine prostate basal and luminal cells are independently self-sustained, but prostate basal cells possess the potential to differentiate into multiple lineages upon induction by embryonic urogenital sinus mesenchyme. Nevertheless, it is unknown how prostate epithelia mature during the postnatal stage. Recently, Ousset et al.展开更多
Although links between cancer and inflammation were fi rstly proposed in the nineteenth century,the molecular mechanism has not yet been clearly understood.Epidemiological studies have identified chronic infections an...Although links between cancer and inflammation were fi rstly proposed in the nineteenth century,the molecular mechanism has not yet been clearly understood.Epidemiological studies have identified chronic infections and infl ammation as major risk factors for various types of cancer.NF-κB transcription factors and the signaling pathways are central coordinators in innate and adaptive immune responses.STAT3 regulates the expression of a variety of genes in response to cellular stimuli,and thus plays a key role in cell growth and apoptosis.Recently,roles of NF-κB and STAT3 in colon,gastric and liver cancers have been extensively investigated.The activation and interaction between STAT3 and NF-κB play vital roles in control of the communication between cancer cells and infl ammatory cells.NF-κB and STAT3 are two major factors controlling the ability of pre-neoplastic and malignant cells to resist apoptosis-based tumor-surveillance and regulating tumor angiogenesis and invasiveness.Understanding the molecular mechanisms of NF-κB and STAT3 cooperation in cancer will offer opportunities for the design of new chemo-preventive and chemotherapeutic approaches.展开更多
Osteosarcoma is a malignant bone tumor that commonly occurs in the pediatric population.Despite the use of chemotherapy and surgery,metastasis remains to be the leading cause of death in patients with osteosarcoma.We ...Osteosarcoma is a malignant bone tumor that commonly occurs in the pediatric population.Despite the use of chemotherapy and surgery,metastasis remains to be the leading cause of death in patients with osteosarcoma.We have previously reported that cytoplasmic mislocalization of p27 is associated with a poor outcome in osteosarcoma.In this study,we further show that lysyl oxidase(LOx)expression was associated with p27 mislocalization.Lox is an enigmatic molecule that acts as a tumor suppressor or a metastatic promoter;however,its role in osteosarcoma is still unclear.Hence,we performed both in vitro and in vivo analyses to dissect the role of Lox in osteosarcoma.The result of our survival analysis indicated that Lox expression significantly correlated with a poor outcome in osteosarcoma with or without controlling for the initial metastasis status(P<0.05).Functionally,we found that higher LoX expression promoted osteosarcoma cell proliferation,migration,and invasiveness in vitro and produced a higher number of mice with pulmonary metastases in an orthotopic xenograft mouse model.Mechanistically,phospho-FAK was increased in osteosarcoma cells with high LOX expression.Our results further showed that FAK inhibition significantly reduced tumor cell proliferation and migration in vitro as well as LoX-mediated metastasis in mice.Together,our findings suggest that there is a novel link between p27 mislocalization and LOX expression.LOX plays a pivotal role in osteosarcoma metastasis by upregulating FAK phosphorylation.FAK inhibition may constitute a promising therapeutic strategy to reduce the development of metastasis in osteosarcoma with Lox overexpression.展开更多
Growth factor receptors （GFRs） are often aberrantly expressed in tumor cells, and altered GFR expressionand activity contribute to the pathogenesis of many types of cancer. A variety of mechanisms have been identifi...Growth factor receptors （GFRs） are often aberrantly expressed in tumor cells, and altered GFR expressionand activity contribute to the pathogenesis of many types of cancer. A variety of mechanisms have been identified that result in enhanced GFR expression and activity in cancer cells. Defects in the pathways responsible for GFR internalization and intraceilular trafficking are likely to be involved in altered GFR expression in a variety of cancers. The roles of GFR trafficking pathways in the regulation of GFR expression, in the pathogenesis of tumors, and in the response of tumors to treatment have not been fully delineated, but the likely contributions of GFR signaling to the development and progression of various malignancies suggest that therapies that modify GFR trafficking may be effective as anticancer treatments. The intraceHular trafficking of GFRs is regulated by a number of protein complexes and by protein ubiquitination. Many of the proteins required for this trafficking are products of tumor suppressor genes, and the expression and function of the protein machinery utilized for intracellular trafficking is frequently altered in tumor cells, consistent with the likely role of GFR trafficking in tumorigenesis. Many of the proteins involved in GFR trafficking have been identified as potential targets for anticancer treatment, and novel treatments directed against these targets are currently in preclinical development and in clinical trials. Ubiquitin ligases are critical for GFR trafficking and represent potentially important targets for the development of novel therapies. The genes for the ubiquitin ligases c-Cbl and UBE4B are located in chromosome regions commonly altered in a variety of tumors and therefore are likely to be important for tumorigenesis, c-Cbl nbiquitinates a number of GFRs and directs them for degradation. Mutations in c-Cbl have been identified in cases of myeloid leukemia and myelodysplasia, providing a link between GFR ubiquitination and trafficking and leukemogenesis. We have shown that UBE4B plays a crucial role in GFR trafficking and degradation in tumor cells, suggesting a previously uncharacterized link between UBE4B and tumorigenesis. With the critical need for new and effective therapies for pediatric malignancies, the recently identified roles for the GFR trafficking pathway in the pathogenesis of various forms of cancer confirm the importance of the further development of novel therapies targeting this pathway in children with cancer.展开更多
Cancer initiation and progression are usually triggered by protooncogene activation and/or tumor suppressor gene inactivation and promoted by further genomic and epigenetic alterations that reprogram cell gene express...Cancer initiation and progression are usually triggered by protooncogene activation and/or tumor suppressor gene inactivation and promoted by further genomic and epigenetic alterations that reprogram cell gene expression,metabolism,proliferation,differentiation,and behavior.Overexpressed or mutation-activated tyrosine kinase receptors and their signaling components,such as HER2,EGFR,Src,RAS,PI3K,and AKT,steroid hormone receptors,such as estrogen receptor and androgen receptor,and other cell growth and cell cycle regulators induce carcinogenesis or promote cancer cell growth,survival,and progression.Accordingly,many therapeutic drugs have been developed and used to target these molecules for treating different cancers(Supplementary Table S1).Although these drugs have significantly improved cancer treatments,most oncogenic factors are also expressed in normal cells and required for normal physiological functions.Therefore,the drugs of anti-oncogenic factors also result in severe adverse effects on cancer patients.An ideal anti-cancer drug should specifically kill cancer cells without affecting normal cellular function,which requires identifying targets essential for cancer cells but non-essential for normal cells.Importantly,these cancer-selective targets required for cancer cell survival may or may not be the classic oncogenes that have attracted extensive attention for drug development.展开更多
Breast cancer cells may disseminate early, before tumor diagnosis. Disseminated tumor cells, or DTCs, reside in the bone marrow, and may persist for years or even decades. Some of these cells may be re-activated to re...Breast cancer cells may disseminate early, before tumor diagnosis. Disseminated tumor cells, or DTCs, reside in the bone marrow, and may persist for years or even decades. Some of these cells may be re-activated to resume aggressive growth, and eventually become overt bone metastases. Recent studies have begun to shed light on this complicated process and revealed multiple steps and intermediate states of colonizing DTCs. However, how cancer-host interactions evolve during this process needs to be further understood. Most of our current knowledge of the bone microenvironment is obtained through studies looking for the hematopoietic stem cell(HSC) niche. Although this long-standing question has not yet been resolved, our search for the HSC niche has resulted in a detailed map of various cell types in the bone marrow. Furthermore, various techniques used to find the HSC niche may also be adapted for finding the cancer cell niche. In this article, we will review the recent progress in both the DTC and HSC areas with a focus on their potential microenvironment niches. We will also discuss how to apply what we have learned from HSC studies to map DTCs in the bone context. We hope to stimulate thoughts and ideas to further elucidate the bone colonization process, and develop potential therapeutic interventions.展开更多
Pluripotent stem cells （PSCs） have the potential to pro- duce any types of cells from all three basic germ layers and the capacity to self-renew and proliferate indefinitely in vitro. The two main types of PSCs, emb...Pluripotent stem cells （PSCs） have the potential to pro- duce any types of cells from all three basic germ layers and the capacity to self-renew and proliferate indefinitely in vitro. The two main types of PSCs, embryonic stem cells （ESCs） and induced pluripotent stem cells （iPSCs）, share common features such as colony morphology, high expression of Oct4 and Nanog, and strong alkaline phosphatase activity. In recent years, increasing evi- dences suggest that telomere length represents another important internal factor in maintaining stem cell pluri- potency. Telomere length homeostasis and its structural integrity help to protect chromosome ends from recom- bination, end fusion, and DNA damage responses, ensuring the divisional ability of mammalian cells. PSCs generally exhibit high telomerase activity to maintain their extremely long and stable telomeres, and emerging data indicate the alternative lengthening of telomeres （ALT） pathway may play an important role in telomere functions too. Such characteristics are likely key to their abilities to differentiate into diverse cell types in v/vo. In this review, we will focus on the function and regulation of telomeres in ESCs and iPSCs, thereby shedding light on the importance of telomere length to pluripotency and the mechanisms that regulate telomeres in PSCs.展开更多
Telomeres, the ends of linear eukaryotic chromosomes, are tandem DNA repeats and capped by various telomeric proteins. These nucleoprotein complexes protect telomeres from DNA damage response （DDR）, recombination, a...Telomeres, the ends of linear eukaryotic chromosomes, are tandem DNA repeats and capped by various telomeric proteins. These nucleoprotein complexes protect telomeres from DNA damage response （DDR）, recombination, and end-to-end fusions, ensuring genome stability. The human telosome/shelterin complex is one of the best-studied telomere-associated protein complexes, made up of six core telomeric proteins TRF1, TRF2, TIN2, RAPI, POT1, and TPPI. TPP1, also known as adrenocortical dysplasia protein homolog （ACD）, is a putative mammalian homolog of TEBP-β and belongs to the oligonucleotide binding （OB）-fold-containing protein family. Three functional domains have been identified within TPP1, the N-terminal OB fold, the POT1 binding recruitment domain （RD）, and the carboxyl-terminal TIN2-interacting domain （TID）. TPP1 can interact with both POT1 and TIN2 to maintain telomere structure, and mediate telomerase recruitment for telomere elongation. These features have indicated TPP1 play an essential role in telomere maintenance. Here, we will review important findings that highlight the functional significance of TPP1, with a focus on its interaction with other telosome components and the telomerase. We will also discuss potential implications in disease therapies.展开更多
Transposons are sequence elements widely distributed among genomes of all three kingdoms of life, providing genomic changes and playing significant roles in genome evolution. Trichomonas vaginalis is an excellent mode...Transposons are sequence elements widely distributed among genomes of all three kingdoms of life, providing genomic changes and playing significant roles in genome evolution. Trichomonas vaginalis is an excellent model system for transposon study since its genome （- 160 Mb） has been sequenced and is composed of - 65% transposons and other repetitive elements. In this study, we primarily report the identification of Kolobok-type transposons （termed tvBac） in T. vaginalis and the results of transposase sequence analysis. We categorized 24 novel subfamilies of the Kolobok element, including one autonomous subfamily and 23 non-autonomous subfamilies. We also identified a novel H2CH motif in tvBac transposases based on multiple sequence alignment. In addition, we supposed that tvBac and Mutator transposons may have evolved independently from a common ancestor according to our phylogenetic analysis. Our results provide basic information for the understanding of the function and evolution of tvBac transposons in particular and other related transposon families in general.展开更多
基金supported by grants from the National Natural Science Foundation of China(NSFC)[81902212,81725010,81672119,81991512]Strategic Priority Research Program of the Chinese Academy of Sciences[XDB19000000]Major Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone[ZJ2018-ZD-004].
文摘Chondrocyte differentiation is a critical process for endochondral ossification,which is responsible for long bone development and fracture repair.Considerable progress has been made in understanding the transcriptional control of chondrocyte differentiation;however,epigenetic regulation of chondrocyte differentiation remains to be further studied.NSD1 is a H3K36(histone H3 at lysine 36)methyltransferase.Here,we showed that mice with Nsd1 deficiency in Prx1+mesenchymal progenitors but not in Col2+chondrocytes showed impaired skeletal growth and fracture healing accompanied by decreased chondrogenic differentiation.Via combined RNA sequencing(RNA-seq)and chromatin immunoprecipitation sequencing(ChIP-seq)analysis,we identified sex determining region Y box 9(Sox9),the key transcription factor of chondrogenic differentiation,as a functional target gene of NSD1.Mechanistically,NSD1 regulates Sox9 expression by modulating H3K36me1 and H3K36me2 levels in the Sox9 promoter region,constituting a novel epigenetic regulatory mechanism of chondrogenesis.Moreover,we found that NSD1 can directly activate the expression of hypoxia-inducible factor 1α(HIF1α),which plays a vital role in chondrogenic differentiation through its regulation of Sox9 expression.Collectively,the results of our study reveal crucial roles of NSD1 in regulating chondrogenic differentiation,skeletal growth,and fracture repair and expand our understanding of the function of epigenetic regulation in chondrogenesis and skeletal biology.
文摘Previous studies demonstrated that adult murine prostate basal and luminal cells are independently self-sustained, but prostate basal cells possess the potential to differentiate into multiple lineages upon induction by embryonic urogenital sinus mesenchyme. Nevertheless, it is unknown how prostate epithelia mature during the postnatal stage. Recently, Ousset et al.
基金supported by the NIH/NINDS grant 1R01NS072420-01.
文摘Although links between cancer and inflammation were fi rstly proposed in the nineteenth century,the molecular mechanism has not yet been clearly understood.Epidemiological studies have identified chronic infections and infl ammation as major risk factors for various types of cancer.NF-κB transcription factors and the signaling pathways are central coordinators in innate and adaptive immune responses.STAT3 regulates the expression of a variety of genes in response to cellular stimuli,and thus plays a key role in cell growth and apoptosis.Recently,roles of NF-κB and STAT3 in colon,gastric and liver cancers have been extensively investigated.The activation and interaction between STAT3 and NF-κB play vital roles in control of the communication between cancer cells and infl ammatory cells.NF-κB and STAT3 are two major factors controlling the ability of pre-neoplastic and malignant cells to resist apoptosis-based tumor-surveillance and regulating tumor angiogenesis and invasiveness.Understanding the molecular mechanisms of NF-κB and STAT3 cooperation in cancer will offer opportunities for the design of new chemo-preventive and chemotherapeutic approaches.
基金This work was partly supported by funding from Sarcoma Alliance for Research through Collaboration(SARC)/National Cancer Institute(No.U54CA168512)the National Institute of Child Health and Human Development(No.R01 HD074553)to TKM.
文摘Osteosarcoma is a malignant bone tumor that commonly occurs in the pediatric population.Despite the use of chemotherapy and surgery,metastasis remains to be the leading cause of death in patients with osteosarcoma.We have previously reported that cytoplasmic mislocalization of p27 is associated with a poor outcome in osteosarcoma.In this study,we further show that lysyl oxidase(LOx)expression was associated with p27 mislocalization.Lox is an enigmatic molecule that acts as a tumor suppressor or a metastatic promoter;however,its role in osteosarcoma is still unclear.Hence,we performed both in vitro and in vivo analyses to dissect the role of Lox in osteosarcoma.The result of our survival analysis indicated that Lox expression significantly correlated with a poor outcome in osteosarcoma with or without controlling for the initial metastasis status(P<0.05).Functionally,we found that higher LoX expression promoted osteosarcoma cell proliferation,migration,and invasiveness in vitro and produced a higher number of mice with pulmonary metastases in an orthotopic xenograft mouse model.Mechanistically,phospho-FAK was increased in osteosarcoma cells with high LOX expression.Our results further showed that FAK inhibition significantly reduced tumor cell proliferation and migration in vitro as well as LoX-mediated metastasis in mice.Together,our findings suggest that there is a novel link between p27 mislocalization and LOX expression.LOX plays a pivotal role in osteosarcoma metastasis by upregulating FAK phosphorylation.FAK inhibition may constitute a promising therapeutic strategy to reduce the development of metastasis in osteosarcoma with Lox overexpression.
文摘Growth factor receptors （GFRs） are often aberrantly expressed in tumor cells, and altered GFR expressionand activity contribute to the pathogenesis of many types of cancer. A variety of mechanisms have been identified that result in enhanced GFR expression and activity in cancer cells. Defects in the pathways responsible for GFR internalization and intraceilular trafficking are likely to be involved in altered GFR expression in a variety of cancers. The roles of GFR trafficking pathways in the regulation of GFR expression, in the pathogenesis of tumors, and in the response of tumors to treatment have not been fully delineated, but the likely contributions of GFR signaling to the development and progression of various malignancies suggest that therapies that modify GFR trafficking may be effective as anticancer treatments. The intraceHular trafficking of GFRs is regulated by a number of protein complexes and by protein ubiquitination. Many of the proteins required for this trafficking are products of tumor suppressor genes, and the expression and function of the protein machinery utilized for intracellular trafficking is frequently altered in tumor cells, consistent with the likely role of GFR trafficking in tumorigenesis. Many of the proteins involved in GFR trafficking have been identified as potential targets for anticancer treatment, and novel treatments directed against these targets are currently in preclinical development and in clinical trials. Ubiquitin ligases are critical for GFR trafficking and represent potentially important targets for the development of novel therapies. The genes for the ubiquitin ligases c-Cbl and UBE4B are located in chromosome regions commonly altered in a variety of tumors and therefore are likely to be important for tumorigenesis, c-Cbl nbiquitinates a number of GFRs and directs them for degradation. Mutations in c-Cbl have been identified in cases of myeloid leukemia and myelodysplasia, providing a link between GFR ubiquitination and trafficking and leukemogenesis. We have shown that UBE4B plays a crucial role in GFR trafficking and degradation in tumor cells, suggesting a previously uncharacterized link between UBE4B and tumorigenesis. With the critical need for new and effective therapies for pediatric malignancies, the recently identified roles for the GFR trafficking pathway in the pathogenesis of various forms of cancer confirm the importance of the further development of novel therapies targeting this pathway in children with cancer.
基金This work wos partially supported by o National Institutes of Health grant R01 CA293455 to J.X.J.X.is a shareholder of Coactigon,Inc.located in Houston,TX 77030,USA.
文摘Cancer initiation and progression are usually triggered by protooncogene activation and/or tumor suppressor gene inactivation and promoted by further genomic and epigenetic alterations that reprogram cell gene expression,metabolism,proliferation,differentiation,and behavior.Overexpressed or mutation-activated tyrosine kinase receptors and their signaling components,such as HER2,EGFR,Src,RAS,PI3K,and AKT,steroid hormone receptors,such as estrogen receptor and androgen receptor,and other cell growth and cell cycle regulators induce carcinogenesis or promote cancer cell growth,survival,and progression.Accordingly,many therapeutic drugs have been developed and used to target these molecules for treating different cancers(Supplementary Table S1).Although these drugs have significantly improved cancer treatments,most oncogenic factors are also expressed in normal cells and required for normal physiological functions.Therefore,the drugs of anti-oncogenic factors also result in severe adverse effects on cancer patients.An ideal anti-cancer drug should specifically kill cancer cells without affecting normal cellular function,which requires identifying targets essential for cancer cells but non-essential for normal cells.Importantly,these cancer-selective targets required for cancer cell survival may or may not be the classic oncogenes that have attracted extensive attention for drug development.
基金supported by the US Department of Defense DAMD W81XWH-16-1-0073 (Era of Hope Scholarship), NCI CA183878Breast Cancer Research Foundation, Susan G. Komen CCR14298445McNair Medical Institute
文摘Breast cancer cells may disseminate early, before tumor diagnosis. Disseminated tumor cells, or DTCs, reside in the bone marrow, and may persist for years or even decades. Some of these cells may be re-activated to resume aggressive growth, and eventually become overt bone metastases. Recent studies have begun to shed light on this complicated process and revealed multiple steps and intermediate states of colonizing DTCs. However, how cancer-host interactions evolve during this process needs to be further understood. Most of our current knowledge of the bone microenvironment is obtained through studies looking for the hematopoietic stem cell(HSC) niche. Although this long-standing question has not yet been resolved, our search for the HSC niche has resulted in a detailed map of various cell types in the bone marrow. Furthermore, various techniques used to find the HSC niche may also be adapted for finding the cancer cell niche. In this article, we will review the recent progress in both the DTC and HSC areas with a focus on their potential microenvironment niches. We will also discuss how to apply what we have learned from HSC studies to map DTCs in the bone context. We hope to stimulate thoughts and ideas to further elucidate the bone colonization process, and develop potential therapeutic interventions.
文摘Pluripotent stem cells （PSCs） have the potential to pro- duce any types of cells from all three basic germ layers and the capacity to self-renew and proliferate indefinitely in vitro. The two main types of PSCs, embryonic stem cells （ESCs） and induced pluripotent stem cells （iPSCs）, share common features such as colony morphology, high expression of Oct4 and Nanog, and strong alkaline phosphatase activity. In recent years, increasing evi- dences suggest that telomere length represents another important internal factor in maintaining stem cell pluri- potency. Telomere length homeostasis and its structural integrity help to protect chromosome ends from recom- bination, end fusion, and DNA damage responses, ensuring the divisional ability of mammalian cells. PSCs generally exhibit high telomerase activity to maintain their extremely long and stable telomeres, and emerging data indicate the alternative lengthening of telomeres （ALT） pathway may play an important role in telomere functions too. Such characteristics are likely key to their abilities to differentiate into diverse cell types in v/vo. In this review, we will focus on the function and regulation of telomeres in ESCs and iPSCs, thereby shedding light on the importance of telomere length to pluripotency and the mechanisms that regulate telomeres in PSCs.
基金Acknowledgements This study was supported by the National Basic Research Program （973 Program） （Nos. 2012CB911201 and 2010CB945401）, the National Natural Science Foundation （Grant Nos. 31371508, 91019020 and 81330055）, the Introduced Innovative R and D Team of Guangdong Province （No. 201001Y0104687244）, Zhujiang Program of Science and Technology Nova in Guangzhou （No. 2011 J2200082）.
文摘Telomeres, the ends of linear eukaryotic chromosomes, are tandem DNA repeats and capped by various telomeric proteins. These nucleoprotein complexes protect telomeres from DNA damage response （DDR）, recombination, and end-to-end fusions, ensuring genome stability. The human telosome/shelterin complex is one of the best-studied telomere-associated protein complexes, made up of six core telomeric proteins TRF1, TRF2, TIN2, RAPI, POT1, and TPPI. TPP1, also known as adrenocortical dysplasia protein homolog （ACD）, is a putative mammalian homolog of TEBP-β and belongs to the oligonucleotide binding （OB）-fold-containing protein family. Three functional domains have been identified within TPP1, the N-terminal OB fold, the POT1 binding recruitment domain （RD）, and the carboxyl-terminal TIN2-interacting domain （TID）. TPP1 can interact with both POT1 and TIN2 to maintain telomere structure, and mediate telomerase recruitment for telomere elongation. These features have indicated TPP1 play an essential role in telomere maintenance. Here, we will review important findings that highlight the functional significance of TPP1, with a focus on its interaction with other telosome components and the telomerase. We will also discuss potential implications in disease therapies.
基金supported by grants from the National Basic Research Program(973 Program)(Nos.2006CB910401, 2006CB910403 and 2006CB910404) awarded to JY and HSthe Chinese Ministry of Science and Technology,the National Science and Technology Key Project(No. 2008ZX10004-013) awarded to JY
文摘Transposons are sequence elements widely distributed among genomes of all three kingdoms of life, providing genomic changes and playing significant roles in genome evolution. Trichomonas vaginalis is an excellent model system for transposon study since its genome （- 160 Mb） has been sequenced and is composed of - 65% transposons and other repetitive elements. In this study, we primarily report the identification of Kolobok-type transposons （termed tvBac） in T. vaginalis and the results of transposase sequence analysis. We categorized 24 novel subfamilies of the Kolobok element, including one autonomous subfamily and 23 non-autonomous subfamilies. We also identified a novel H2CH motif in tvBac transposases based on multiple sequence alignment. In addition, we supposed that tvBac and Mutator transposons may have evolved independently from a common ancestor according to our phylogenetic analysis. Our results provide basic information for the understanding of the function and evolution of tvBac transposons in particular and other related transposon families in general.
