A thermo-insensitive pale green leaf mutant (pgl2) was isolated from T-DNA inserted transgenic lines of rice (Oryza sativa L. subsp, japonica cv. Nipponbare). Genetic analysis indicated that the phenotype was caus...A thermo-insensitive pale green leaf mutant (pgl2) was isolated from T-DNA inserted transgenic lines of rice (Oryza sativa L. subsp, japonica cv. Nipponbare). Genetic analysis indicated that the phenotype was caused by a recessive mutation in a single nuclear-encoded gene. To map the PGL2gene, an F2 population was constructed by crossing the mutant with Longtefu (Oryza sativa L. subsp, indica). The PGL2 locus was roughly linked to SSR marker RM331 on chromosome 8. To finely map the gene, 14 new InDel markers were developed around the marker, and PGL2 was further mapped to a 2.37 Mb centromeric region. Analysis on chlorophyll contents of leaves showed that there was no obvious difference between the mutant and the wild type in total chlorophyll (Chl) content, while the ratio of Chl a / Chl b in the mutant was only about 1, which was distinctly lower than that in the wild type, suggesting that the PGL2 gene was related to the conversion between Chl a and Chl b. Moreover, the method of primer design around the centromeric region was discussed, which would provide insight into fine mapping of the functional genes in plant centromeres.展开更多
Using indirect immunofluorescence (IIF), an anti-centromere protein CenpG-serum was verified. Western blot of the protein extracts of 31 samples of breast cancer tissues and their normal (not cancerous ) tissues a lit...Using indirect immunofluorescence (IIF), an anti-centromere protein CenpG-serum was verified. Western blot of the protein extracts of 31 samples of breast cancer tissues and their normal (not cancerous ) tissues a little far away from them in the same individuals showed that, in the majority of the tests (71%), centromere protein CenpG over expressed in breast cancer tissues. And moreover, a kind of protein component whose molecular weight is 43 kd, and which can be recognized by anti-CenpG serum was found in two of the cancer samples. The results suggested that CenpG (together whith it, there may be other relative components),which has been found and named recently, may be related to cancer,and its differential expressing is probably related to malignant cell proliferation.展开更多
Breast cancer is one of the leading causes of cancer death worldwide.This study aimed to analyze the expression of centromere protein H(CENP-H) in breast cancer and to correlate it with clinicopathologic data,includin...Breast cancer is one of the leading causes of cancer death worldwide.This study aimed to analyze the expression of centromere protein H(CENP-H) in breast cancer and to correlate it with clinicopathologic data,including patient survival.Using reverse transcription-polymerase chain reaction and Western blotting to detect the expression of CENP-H in normal mammary epithelial cells,immortalized mammary epithelial cell lines,and breast cancer cell lines,we observed that the mRNA and protein levels of CENP-H were higher in breast cancer cell lines and in immortalized mammary epithelial cells than in normal mammary epithelial cells.We next examined CENP-H expression in 307 paraffin-embedded archived samples of clinicopathologically characterized breast cancer using immunohistochemistry,and detected high CENP-H expression in 134(43.6%) samples.Statistical analysis showed that CENP-H expression was related with clinical stage(P = 0.001),T classification(P = 0.032),N classification(P = 0.018),and Ki-67(P < 0.001).Patients with high CENP-H expression had short overall survival.Multivariate analysis showed that CENP-H expression was an independent prognostic indicator for patient survival.Our results suggest that CENP-H protein is a valuable marker of breast cancer progression and prognosis.展开更多
The aneuploid with isochromosome or telochromosome is ideal material for exploring the position of centromere in lingkage map. FOr obtaining these aneuploids in rice, the primary trisomics from triplo-1 to triplo-12 a...The aneuploid with isochromosome or telochromosome is ideal material for exploring the position of centromere in lingkage map. FOr obtaining these aneuploids in rice, the primary trisomics from triplo-1 to triplo-12 and the aneuploids derived from a triploid of indica rice variety Zhongxian 3037 were carefully investigated. From the offsprings of triplo-10, a primary trisomic of chromosome 10 of the variety, an isotetrasomic "triplo-10-1" was obtained. Cytological investigation revealed that a pair of extra isochromosomes of triplo-10-1 were come from the short arm of chromosome 10. In the offsprings of the isotetrasomic, a secondary trisomic "triplo-10-2" 5 in which the extra- chromosome was an isochromosome derived from the short arm of chromosome 10, was identified. With the isotetrasomic, secondary trisomic, primary trisomic and diploid of variety Zhongxian 3037, different molecular markers were used for exploring the position of the centromere of chromosome 10. Based on the DNA dosage effect, it was verified that the molecular markers G1125, G333 and L169 were located on the short arm, G1084 and other 16 available molecular markers were on the long arm of chromosome 10. So the centromere of chromosome 10 was located somewhere betweenG1125 and G1084 according to the RFLP linkage map given by Kurata et al[1]. The distance from G1125 to G1084 was about 3.2cM.展开更多
Recently the antichromosome antisera from several scleroderma patients have been found to recognize the pellicle of metaphase and anaphase chromosomes. In order to identify the pellicle components, we used these antic...Recently the antichromosome antisera from several scleroderma patients have been found to recognize the pellicle of metaphase and anaphase chromosomes. In order to identify the pellicle components, we used these antichromosome antisera to screen a human embryonic cDNA library. The sequences of the positive clones are identical to the cDNA gene sequence of CENP-C (centromere protein C), a human centromere autoantigen. This result suggusts that CENP-C is a component of the pellicle of human metaphase and anaphase chromosomes.展开更多
目的:探讨血清抗着丝粒蛋白F抗体(anti-centromere protein F antibody,anti-CENPF)在乳腺癌中的临床价值。方法:收集100例初诊乳腺癌(breast cancer,BC)患者、40例乳腺良性疾病(non breast cancer,non-BC)患者和40名健康体检者(healthy...目的:探讨血清抗着丝粒蛋白F抗体(anti-centromere protein F antibody,anti-CENPF)在乳腺癌中的临床价值。方法:收集100例初诊乳腺癌(breast cancer,BC)患者、40例乳腺良性疾病(non breast cancer,non-BC)患者和40名健康体检者(healthy control,HC)血清,采用酶联免疫吸附试验检测血清中的anti-CENPF水平,同时化学发光法测定血清糖类抗原153(carbohydrate antigen 153,CA153)的水平。结果:BC组血清anti-CENPF水平高于non-BC组和HC组,差异有统计学意义(P<0.05)。anti-CENPF和CA153诊断乳腺癌中的曲线下面积(area under the curve,AUC)分别为0.714和0.672,两者联合检测的AUC为0.739。有淋巴结转移、远处转移或者人表皮生长因子受体2(human epidermal growth factor receptor-2,HER-2)阴性的乳腺癌患者血清anti-CENPF浓度明显升高(P<0.05)。不同肿瘤大小、临床分期、分子分型乳腺癌患者血清anti-CENPF水平比较,差异有统计学意义(P<0.05)。组间比较显示Ⅳ期和Ⅲ期血清anti-CENPF浓度高于Ⅰ期和Ⅱ期,HER-2过表达型、Luminal B型血清anti-CENPF水平低于三阴性乳腺癌(triple negative breast cancer,TNBC)患者。雌激素受体(receptors estrogen,ER)阳性的乳腺癌患者中,HER-2阴性组的anti-CENPF浓度高于HER-2阳性组,差异有统计学意义(P=0.026)。结论:血清antiCENPF在乳腺癌的诊断、临床分期及分子分型中发挥了重要作用,其水平可能与乳腺癌预后呈负相关,有望成为乳腺癌潜在的疾病标志物。展开更多
Centromere positioning and organization are crucial for genome evolution;however,research on centro-mere biology is largely influenced by the quality of available genome assemblies.Here,we combined Oxford Nanopore and...Centromere positioning and organization are crucial for genome evolution;however,research on centro-mere biology is largely influenced by the quality of available genome assemblies.Here,we combined Oxford Nanopore and Pacific Biosciences technologies to de novo assemble two high-quality reference genomes for Gossypium hirsutum(TM-1)and Gossypium barbadense(3-79).Compared with previously published reference genomes,our assemblies show substantial improvements,with the contig N50 improved by 4.6-fold and 5.6-fold,respectively,and thus represent the most complete cotton genomes to date.These high-quality reference genomes enable us to characterize 14 and 5 complete centromeric regions for G.hirsutum and G.barbadense,respectively.Our data revealed that the centromeres of allotetraploid cotton are occupied by members of the centromeric repeat for maize(CRM)and Tekay long terminal repeat families,and the CRM family reshapes the centromere structure of the At subgenome after polyploidization.These two intertwined families have driven the convergent evolution of centromeres between the two subgenomes,ensuring centromere function and genome stability.In addition,the reposi-tioning and high sequence divergence of centromeres between G.hirsutum and G.barbadense have contributed to speciation and centromere diversity.This study sheds light on centromere evolution in a sig-nificant crop and provides an alternative approach for exploring the evolution of polyploid plants.展开更多
Rice(Oryza sativa)is a significant crop worldwide with a genome shaped by various evolutionary factors.Rice centromeres are crucial for chromosome segregation,and contain some unreported genes.Due to the diverse and c...Rice(Oryza sativa)is a significant crop worldwide with a genome shaped by various evolutionary factors.Rice centromeres are crucial for chromosome segregation,and contain some unreported genes.Due to the diverse and complex centromere region,a comprehensive understanding of rice centromere structure and function at the population level is needed.We constructed a high-quality centromere map based on the rice super pangenome consisting of a 251-accession panel comprising both cultivated and wild species of Asian and African rice.We showed that rice centromeres have diverse satellite repeat CentO,which vary across chromosomes and subpopulations,reflecting their distinct evolutionary patterns.We also revealed that long terminal repeats(LTRs),especially young Gypsy-type LTRs,are abundant in the peripheral CentO-enriched regions and drive rice centromere expansion and evolution.Furthermore,high-quality genome assembly and complete telomere-to-telomere(T2T)reference genome enable us to obtain more centromeric genome information despite mapping and cloning of centromere genes being challenging.We investigated the association between structural variations and gene expression in the rice centromere.A centromere gene,OsMAB,which positively regulates rice tiller number,was further confirmed by expression quantitative trait loci,haplotype analysis and clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein9 methods.By revealing the new insights into the evolutionary patterns and biological roles of rice centromeres,our finding will facilitate future research on centromere biology and crop improvement.展开更多
目的:分析着丝粒蛋白A(centromere protein A,CENP-A)在宫颈癌中的表达情况,与临床病理参数相关性及临床意义。方法:GEPIA和HPA数据库分析CENP-A基因及蛋白在宫颈癌组织中的表达情况;免疫组化检测宫颈癌中CENP-A蛋白的表达水平,分析其...目的:分析着丝粒蛋白A(centromere protein A,CENP-A)在宫颈癌中的表达情况,与临床病理参数相关性及临床意义。方法:GEPIA和HPA数据库分析CENP-A基因及蛋白在宫颈癌组织中的表达情况;免疫组化检测宫颈癌中CENP-A蛋白的表达水平,分析其与临床病理参数之间的关系;使用Linked Omics数据库寻找与CENP-A共表达基因,分析CENP-A可能参与宫颈癌发生发展的信号通路。结果:生物信息学分析显示宫颈癌组织中CENP-A基因和蛋白的表达水平明显高于癌旁组织(P<0.05);免疫组化结果显示宫颈癌组织CENP-A蛋白表达水平显著高于癌旁组织(P<0.05),且与患者的肿瘤分期及浸润程度相关。通过基因共表达分析,KIF2C、CDC20、FAM72B等基因与CENP-A表达呈正相关,PARM1、ABCA9和SYNE1等基因与CENP-A表达呈负相关(FDR<0.05),CENP-A基因参与了细胞周期、DNA复制等途径。结论:CENP-A在宫颈癌组织中高表达,与宫颈癌的预后以及发生发展相关。展开更多
目的旨在探讨着丝粒蛋白U(centromere protein U,CENPU)在结直肠癌患者肠组织中的表达情况,并结合生物信息学分析其表达水平对结直肠癌患者预后的影响。方法通过实时荧光定量聚合酶链反应(quantitative real time polymerase chain reac...目的旨在探讨着丝粒蛋白U(centromere protein U,CENPU)在结直肠癌患者肠组织中的表达情况,并结合生物信息学分析其表达水平对结直肠癌患者预后的影响。方法通过实时荧光定量聚合酶链反应(quantitative real time polymerase chain reaction,qRT-PCR)、蛋白质免疫印迹(Western blot,WB)法以及免疫组织化学染色(immunohistochemistry,IHC)实验验证CENPU在组织中的表达情况。结合患者临床病例资料,通过单因素和多因素Cox回归分析CENPU的表达与结直肠癌患者临床病例参数的相关性;然后通过绘制受试操作者操作特征(receiver operating characteristic,ROC)曲线和Kaplan-Meier生存曲线,探究CENPU的表达对结直肠癌患者预后的预测作用。最后,通过生物信息学分析CENPU的表达对结直肠癌疾病进展影响的可能分子机制。结果通过qRT-PCR、WB法以及IHC实验均发现,与正常组织比较,CENPU在结直肠癌患者癌组织中表达显著升高。Cox回归分析表明CENPU的表达与患者的年龄和TNM分期显著相关,是影响患者预后的危险因素。Kaplan-Meier生存曲线分析表明:CENPU高表达的结直肠癌患者的生存率显著降低。ROC曲线结果表明:基于CENPU的表达建立的模型具有较高的预测结直肠癌患者预后的能力。生物信息学分析结果表明:CENPI、CENPN、CENPD、CENPK、CENPP、CENPM、CENPQ、CENPH、NDC80以及ITGB3BP这10个基因与CENPU基因具有相互作用关系;CENPU参与DNA修复、MYC/TARGETS/V1以及PI3K/AKT/MTOR等信号通路。结论结直肠癌患者癌组织中高表达的CENPU与患者的不良预后显著相关,提示CENPU有望成为结直肠癌患者早期诊断及预测预后的潜在靶点。展开更多
Centromeres play a vital role in cellular division by facilitating kinetochore assembly and spindle attachments.Despite their conserved functionality,centromeric DNA sequences exhibit rapid evolution,presenting divers...Centromeres play a vital role in cellular division by facilitating kinetochore assembly and spindle attachments.Despite their conserved functionality,centromeric DNA sequences exhibit rapid evolution,presenting diverse sizes and compositions across species.The functional significance of rye centromeric DNA sequences,particularly in centromere identity,remains unclear.In this study,we comprehensively characterized the sequence composition and organization of rye centromeres.Our findings revealed that these centromeres are primarily composed of long terminal repeat retrotransposons(LTR-RTs)and interspersed minisatellites.We systematically classified LTR-RTs into five categories,highlighting the prevalence of younger CRS1,CRS2,and CRS3 of CRSs(centromeric retrotransposons of Secale cereale)were primarily located in the core centromeres and exhibited a higher association with CENH3 nucleosomes.The minisatellites,mainly derived from retrotransposons,along with CRSs,played a pivotal role in establishing functional centromeres in rye.Additionally,we observed the formation of R-loops at specific regions of CRS1,CRS2,and CRS3,with both rye pericentromeres and centromeres exhibiting enrichment in R-loops.Notably,these R-loops selectively formed at binding regions of the CENH3 nucleosome in rye centromeres,suggesting a potential role in mediating the precise loading of CENH3 to centromeres and contributing to centromere specification.Our work provides insights into the DNA sequence composition,distribution,and potential function of R-loops in rye centromeres.This knowledge contributes valuable information to understanding the genetics and epigenetics of rye centromeres,offering implications for the development of synthetic centromeres in future plant modifications and beyond.展开更多
The Triticum-Aegilops complex groups demonstrated high cross-affinity with each other to overcome the barriers of distant hybridization(Loureiro et al.,2023).Distant hybridization involves two distinct yet closely rel...The Triticum-Aegilops complex groups demonstrated high cross-affinity with each other to overcome the barriers of distant hybridization(Loureiro et al.,2023).Distant hybridization involves two distinct yet closely related events:hybridization and genome doubling.Previous studies have indicated that bursts of transposable elements(TEs)can occur as a consequence or concomitant to hybridization or genome duplication(Parisod et al.,2010).This raises an important scientific question regarding how the TEs-rich centromere region copes with genomic shock(McClintock,1984).The Triticum-Aegilops species complexes,particularly in the F1,So,and subsequent early generations resulting from successive selfcrossing,offer an opportunity to investigate whether the centromere environment undergoes reconstruction and the associated mechanisms that maintain genomic stability.展开更多
Non-B-form DNA differs from the classic B-DNA double helix structure and plays a crucial regulatory role in replication and transcription.However,the role of non-B-form DNA in centromeres,especially in polyploid wheat...Non-B-form DNA differs from the classic B-DNA double helix structure and plays a crucial regulatory role in replication and transcription.However,the role of non-B-form DNA in centromeres,especially in polyploid wheat,remains elusive.Here,we systematically analyzed seven non-B-form DNA motif profiles(A-phased DNA repeat,direct repeat,G-quadruplex,inverted repeat,mirror repeat,short tandem repeat,and Z-DNA)in hexaploid wheat.We found that three of these non-B-form DNA motifs were enriched at centromeric regions,especially at the CENH3-binding sites,suggesting that non-B-form DNA may create a favorable loading environment for the CENH3 nucleosome.To investigate the dynamics of centromeric non-B form DNA during the alloploidization process,we analyzed DNA secondary structure using CENH3 ChIP-seq data from newly formed allotetraploid wheat and its two diploid ancestors.We found that newly formed allotetraploid wheat formed more non-B-form DNA in centromeric regions compared with their parents,suggesting that non-B-form DNA is related to the localization of the centromeric regions in newly formed wheat.Furthermore,non-B-form DNA enriched in the centromeric regions was found to preferentially form on young LTR retrotransposons,explaining CENH3's tendency to bind to younger LTR.Collectively,our study describes the landscape of non-B-form DNA in the wheat genome,and sheds light on its potential role in the evolution of polyploid centromeres.展开更多
目的:探讨着丝粒蛋白F(centromere protein F,CENPF)在腺样囊性癌(adenoid cystic carcinoma,ACC)发生发展中的作用和分子机制。方法:通过小干扰RNA转染敲低ACC细胞中的CENPF。通过细胞计数试剂盒(cell counting kit-8,CCK-8)、划痕实验...目的:探讨着丝粒蛋白F(centromere protein F,CENPF)在腺样囊性癌(adenoid cystic carcinoma,ACC)发生发展中的作用和分子机制。方法:通过小干扰RNA转染敲低ACC细胞中的CENPF。通过细胞计数试剂盒(cell counting kit-8,CCK-8)、划痕实验和Transwell测定评估敲低CENPF对ACC细胞增殖、迁移、侵袭的影响;通过蛋白免疫印迹实验分析改变CENPF表达后ACC细胞中磷脂酰肌醇-3-激酶(phosphatidylinositol-3-kinase,PI3K)/丝氨酸/苏氨酸蛋白激酶(serine/threonine protein kinase,AKT)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路相关蛋白表达变化,通过CCK-8、划痕实验和Transwell测定评估敲低CENPF联合PI3K抑制剂BKM-120对ACC细胞增殖、迁移、侵袭的影响。结果:敲低ACC-M中CENPF表达后,CCK-8实验证明其增殖能力减弱;划痕实验表明其迁移能力减弱,Transwell实验表明其侵袭能力减弱,PI3K/AKT通路关键蛋白p-PI3K、p-AKT和p-mTOR蛋白表达水平下降。在下调CENPF的ACC-M中加入PI3K抑制剂,PI3K/AKT通路关键蛋白表达水平进一步下降。此外,加入PI3K抑制剂后,CENPF下调的ACC-M增殖、迁移、侵袭能力较单纯下调CENPF的ACC-M进一步减弱。结论:CENPF通过调控PI3K/AKT信号通路参与ACC进展。展开更多
文摘A thermo-insensitive pale green leaf mutant (pgl2) was isolated from T-DNA inserted transgenic lines of rice (Oryza sativa L. subsp, japonica cv. Nipponbare). Genetic analysis indicated that the phenotype was caused by a recessive mutation in a single nuclear-encoded gene. To map the PGL2gene, an F2 population was constructed by crossing the mutant with Longtefu (Oryza sativa L. subsp, indica). The PGL2 locus was roughly linked to SSR marker RM331 on chromosome 8. To finely map the gene, 14 new InDel markers were developed around the marker, and PGL2 was further mapped to a 2.37 Mb centromeric region. Analysis on chlorophyll contents of leaves showed that there was no obvious difference between the mutant and the wild type in total chlorophyll (Chl) content, while the ratio of Chl a / Chl b in the mutant was only about 1, which was distinctly lower than that in the wild type, suggesting that the PGL2 gene was related to the conversion between Chl a and Chl b. Moreover, the method of primer design around the centromeric region was discussed, which would provide insight into fine mapping of the functional genes in plant centromeres.
文摘Using indirect immunofluorescence (IIF), an anti-centromere protein CenpG-serum was verified. Western blot of the protein extracts of 31 samples of breast cancer tissues and their normal (not cancerous ) tissues a little far away from them in the same individuals showed that, in the majority of the tests (71%), centromere protein CenpG over expressed in breast cancer tissues. And moreover, a kind of protein component whose molecular weight is 43 kd, and which can be recognized by anti-CenpG serum was found in two of the cancer samples. The results suggested that CenpG (together whith it, there may be other relative components),which has been found and named recently, may be related to cancer,and its differential expressing is probably related to malignant cell proliferation.
文摘Breast cancer is one of the leading causes of cancer death worldwide.This study aimed to analyze the expression of centromere protein H(CENP-H) in breast cancer and to correlate it with clinicopathologic data,including patient survival.Using reverse transcription-polymerase chain reaction and Western blotting to detect the expression of CENP-H in normal mammary epithelial cells,immortalized mammary epithelial cell lines,and breast cancer cell lines,we observed that the mRNA and protein levels of CENP-H were higher in breast cancer cell lines and in immortalized mammary epithelial cells than in normal mammary epithelial cells.We next examined CENP-H expression in 307 paraffin-embedded archived samples of clinicopathologically characterized breast cancer using immunohistochemistry,and detected high CENP-H expression in 134(43.6%) samples.Statistical analysis showed that CENP-H expression was related with clinical stage(P = 0.001),T classification(P = 0.032),N classification(P = 0.018),and Ki-67(P < 0.001).Patients with high CENP-H expression had short overall survival.Multivariate analysis showed that CENP-H expression was an independent prognostic indicator for patient survival.Our results suggest that CENP-H protein is a valuable marker of breast cancer progression and prognosis.
文摘The aneuploid with isochromosome or telochromosome is ideal material for exploring the position of centromere in lingkage map. FOr obtaining these aneuploids in rice, the primary trisomics from triplo-1 to triplo-12 and the aneuploids derived from a triploid of indica rice variety Zhongxian 3037 were carefully investigated. From the offsprings of triplo-10, a primary trisomic of chromosome 10 of the variety, an isotetrasomic "triplo-10-1" was obtained. Cytological investigation revealed that a pair of extra isochromosomes of triplo-10-1 were come from the short arm of chromosome 10. In the offsprings of the isotetrasomic, a secondary trisomic "triplo-10-2" 5 in which the extra- chromosome was an isochromosome derived from the short arm of chromosome 10, was identified. With the isotetrasomic, secondary trisomic, primary trisomic and diploid of variety Zhongxian 3037, different molecular markers were used for exploring the position of the centromere of chromosome 10. Based on the DNA dosage effect, it was verified that the molecular markers G1125, G333 and L169 were located on the short arm, G1084 and other 16 available molecular markers were on the long arm of chromosome 10. So the centromere of chromosome 10 was located somewhere betweenG1125 and G1084 according to the RFLP linkage map given by Kurata et al[1]. The distance from G1125 to G1084 was about 3.2cM.
文摘Recently the antichromosome antisera from several scleroderma patients have been found to recognize the pellicle of metaphase and anaphase chromosomes. In order to identify the pellicle components, we used these antichromosome antisera to screen a human embryonic cDNA library. The sequences of the positive clones are identical to the cDNA gene sequence of CENP-C (centromere protein C), a human centromere autoantigen. This result suggusts that CENP-C is a component of the pellicle of human metaphase and anaphase chromosomes.
文摘目的:探讨血清抗着丝粒蛋白F抗体(anti-centromere protein F antibody,anti-CENPF)在乳腺癌中的临床价值。方法:收集100例初诊乳腺癌(breast cancer,BC)患者、40例乳腺良性疾病(non breast cancer,non-BC)患者和40名健康体检者(healthy control,HC)血清,采用酶联免疫吸附试验检测血清中的anti-CENPF水平,同时化学发光法测定血清糖类抗原153(carbohydrate antigen 153,CA153)的水平。结果:BC组血清anti-CENPF水平高于non-BC组和HC组,差异有统计学意义(P<0.05)。anti-CENPF和CA153诊断乳腺癌中的曲线下面积(area under the curve,AUC)分别为0.714和0.672,两者联合检测的AUC为0.739。有淋巴结转移、远处转移或者人表皮生长因子受体2(human epidermal growth factor receptor-2,HER-2)阴性的乳腺癌患者血清anti-CENPF浓度明显升高(P<0.05)。不同肿瘤大小、临床分期、分子分型乳腺癌患者血清anti-CENPF水平比较,差异有统计学意义(P<0.05)。组间比较显示Ⅳ期和Ⅲ期血清anti-CENPF浓度高于Ⅰ期和Ⅱ期,HER-2过表达型、Luminal B型血清anti-CENPF水平低于三阴性乳腺癌(triple negative breast cancer,TNBC)患者。雌激素受体(receptors estrogen,ER)阳性的乳腺癌患者中,HER-2阴性组的anti-CENPF浓度高于HER-2阳性组,差异有统计学意义(P=0.026)。结论:血清antiCENPF在乳腺癌的诊断、临床分期及分子分型中发挥了重要作用,其水平可能与乳腺癌预后呈负相关,有望成为乳腺癌潜在的疾病标志物。
基金supported by the National Natural Science Foundation of China (32170645)the National Key Research and Development Program of China (2021YFF1000900).
文摘Centromere positioning and organization are crucial for genome evolution;however,research on centro-mere biology is largely influenced by the quality of available genome assemblies.Here,we combined Oxford Nanopore and Pacific Biosciences technologies to de novo assemble two high-quality reference genomes for Gossypium hirsutum(TM-1)and Gossypium barbadense(3-79).Compared with previously published reference genomes,our assemblies show substantial improvements,with the contig N50 improved by 4.6-fold and 5.6-fold,respectively,and thus represent the most complete cotton genomes to date.These high-quality reference genomes enable us to characterize 14 and 5 complete centromeric regions for G.hirsutum and G.barbadense,respectively.Our data revealed that the centromeres of allotetraploid cotton are occupied by members of the centromeric repeat for maize(CRM)and Tekay long terminal repeat families,and the CRM family reshapes the centromere structure of the At subgenome after polyploidization.These two intertwined families have driven the convergent evolution of centromeres between the two subgenomes,ensuring centromere function and genome stability.In addition,the reposi-tioning and high sequence divergence of centromeres between G.hirsutum and G.barbadense have contributed to speciation and centromere diversity.This study sheds light on centromere evolution in a sig-nificant crop and provides an alternative approach for exploring the evolution of polyploid plants.
基金supported by the National Natural Science Foundation of China(32188102,32372148)Innovation Program of Chinese Academy of Agricultural Sciences,the Youth Innovation of Chinese Academy of Agricultural Sciences(Y20230C36)+1 种基金Guangdong Basic and Applied Basic Research Foundation(2023B1515020053)the Youth Program of Guangdong Basic and Applied Research(2021A1515111123)。
文摘Rice(Oryza sativa)is a significant crop worldwide with a genome shaped by various evolutionary factors.Rice centromeres are crucial for chromosome segregation,and contain some unreported genes.Due to the diverse and complex centromere region,a comprehensive understanding of rice centromere structure and function at the population level is needed.We constructed a high-quality centromere map based on the rice super pangenome consisting of a 251-accession panel comprising both cultivated and wild species of Asian and African rice.We showed that rice centromeres have diverse satellite repeat CentO,which vary across chromosomes and subpopulations,reflecting their distinct evolutionary patterns.We also revealed that long terminal repeats(LTRs),especially young Gypsy-type LTRs,are abundant in the peripheral CentO-enriched regions and drive rice centromere expansion and evolution.Furthermore,high-quality genome assembly and complete telomere-to-telomere(T2T)reference genome enable us to obtain more centromeric genome information despite mapping and cloning of centromere genes being challenging.We investigated the association between structural variations and gene expression in the rice centromere.A centromere gene,OsMAB,which positively regulates rice tiller number,was further confirmed by expression quantitative trait loci,haplotype analysis and clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein9 methods.By revealing the new insights into the evolutionary patterns and biological roles of rice centromeres,our finding will facilitate future research on centromere biology and crop improvement.
文摘目的:分析着丝粒蛋白A(centromere protein A,CENP-A)在宫颈癌中的表达情况,与临床病理参数相关性及临床意义。方法:GEPIA和HPA数据库分析CENP-A基因及蛋白在宫颈癌组织中的表达情况;免疫组化检测宫颈癌中CENP-A蛋白的表达水平,分析其与临床病理参数之间的关系;使用Linked Omics数据库寻找与CENP-A共表达基因,分析CENP-A可能参与宫颈癌发生发展的信号通路。结果:生物信息学分析显示宫颈癌组织中CENP-A基因和蛋白的表达水平明显高于癌旁组织(P<0.05);免疫组化结果显示宫颈癌组织CENP-A蛋白表达水平显著高于癌旁组织(P<0.05),且与患者的肿瘤分期及浸润程度相关。通过基因共表达分析,KIF2C、CDC20、FAM72B等基因与CENP-A表达呈正相关,PARM1、ABCA9和SYNE1等基因与CENP-A表达呈负相关(FDR<0.05),CENP-A基因参与了细胞周期、DNA复制等途径。结论:CENP-A在宫颈癌组织中高表达,与宫颈癌的预后以及发生发展相关。
文摘目的旨在探讨着丝粒蛋白U(centromere protein U,CENPU)在结直肠癌患者肠组织中的表达情况,并结合生物信息学分析其表达水平对结直肠癌患者预后的影响。方法通过实时荧光定量聚合酶链反应(quantitative real time polymerase chain reaction,qRT-PCR)、蛋白质免疫印迹(Western blot,WB)法以及免疫组织化学染色(immunohistochemistry,IHC)实验验证CENPU在组织中的表达情况。结合患者临床病例资料,通过单因素和多因素Cox回归分析CENPU的表达与结直肠癌患者临床病例参数的相关性;然后通过绘制受试操作者操作特征(receiver operating characteristic,ROC)曲线和Kaplan-Meier生存曲线,探究CENPU的表达对结直肠癌患者预后的预测作用。最后,通过生物信息学分析CENPU的表达对结直肠癌疾病进展影响的可能分子机制。结果通过qRT-PCR、WB法以及IHC实验均发现,与正常组织比较,CENPU在结直肠癌患者癌组织中表达显著升高。Cox回归分析表明CENPU的表达与患者的年龄和TNM分期显著相关,是影响患者预后的危险因素。Kaplan-Meier生存曲线分析表明:CENPU高表达的结直肠癌患者的生存率显著降低。ROC曲线结果表明:基于CENPU的表达建立的模型具有较高的预测结直肠癌患者预后的能力。生物信息学分析结果表明:CENPI、CENPN、CENPD、CENPK、CENPP、CENPM、CENPQ、CENPH、NDC80以及ITGB3BP这10个基因与CENPU基因具有相互作用关系;CENPU参与DNA修复、MYC/TARGETS/V1以及PI3K/AKT/MTOR等信号通路。结论结直肠癌患者癌组织中高表达的CENPU与患者的不良预后显著相关,提示CENPU有望成为结直肠癌患者早期诊断及预测预后的潜在靶点。
基金supported by the National Natural Science Foundation of China(31991212,31920103006)。
文摘Centromeres play a vital role in cellular division by facilitating kinetochore assembly and spindle attachments.Despite their conserved functionality,centromeric DNA sequences exhibit rapid evolution,presenting diverse sizes and compositions across species.The functional significance of rye centromeric DNA sequences,particularly in centromere identity,remains unclear.In this study,we comprehensively characterized the sequence composition and organization of rye centromeres.Our findings revealed that these centromeres are primarily composed of long terminal repeat retrotransposons(LTR-RTs)and interspersed minisatellites.We systematically classified LTR-RTs into five categories,highlighting the prevalence of younger CRS1,CRS2,and CRS3 of CRSs(centromeric retrotransposons of Secale cereale)were primarily located in the core centromeres and exhibited a higher association with CENH3 nucleosomes.The minisatellites,mainly derived from retrotransposons,along with CRSs,played a pivotal role in establishing functional centromeres in rye.Additionally,we observed the formation of R-loops at specific regions of CRS1,CRS2,and CRS3,with both rye pericentromeres and centromeres exhibiting enrichment in R-loops.Notably,these R-loops selectively formed at binding regions of the CENH3 nucleosome in rye centromeres,suggesting a potential role in mediating the precise loading of CENH3 to centromeres and contributing to centromere specification.Our work provides insights into the DNA sequence composition,distribution,and potential function of R-loops in rye centromeres.This knowledge contributes valuable information to understanding the genetics and epigenetics of rye centromeres,offering implications for the development of synthetic centromeres in future plant modifications and beyond.
基金the National Natural Science Foundation of China(31991212)the National Key Research and Development Program of China(2022YFF1003303).
文摘The Triticum-Aegilops complex groups demonstrated high cross-affinity with each other to overcome the barriers of distant hybridization(Loureiro et al.,2023).Distant hybridization involves two distinct yet closely related events:hybridization and genome doubling.Previous studies have indicated that bursts of transposable elements(TEs)can occur as a consequence or concomitant to hybridization or genome duplication(Parisod et al.,2010).This raises an important scientific question regarding how the TEs-rich centromere region copes with genomic shock(McClintock,1984).The Triticum-Aegilops species complexes,particularly in the F1,So,and subsequent early generations resulting from successive selfcrossing,offer an opportunity to investigate whether the centromere environment undergoes reconstruction and the associated mechanisms that maintain genomic stability.
基金supported by the National Natural Science Foundation of China(31991212)the National Key Research and Development Program of China(2022YFF1003303)。
文摘Non-B-form DNA differs from the classic B-DNA double helix structure and plays a crucial regulatory role in replication and transcription.However,the role of non-B-form DNA in centromeres,especially in polyploid wheat,remains elusive.Here,we systematically analyzed seven non-B-form DNA motif profiles(A-phased DNA repeat,direct repeat,G-quadruplex,inverted repeat,mirror repeat,short tandem repeat,and Z-DNA)in hexaploid wheat.We found that three of these non-B-form DNA motifs were enriched at centromeric regions,especially at the CENH3-binding sites,suggesting that non-B-form DNA may create a favorable loading environment for the CENH3 nucleosome.To investigate the dynamics of centromeric non-B form DNA during the alloploidization process,we analyzed DNA secondary structure using CENH3 ChIP-seq data from newly formed allotetraploid wheat and its two diploid ancestors.We found that newly formed allotetraploid wheat formed more non-B-form DNA in centromeric regions compared with their parents,suggesting that non-B-form DNA is related to the localization of the centromeric regions in newly formed wheat.Furthermore,non-B-form DNA enriched in the centromeric regions was found to preferentially form on young LTR retrotransposons,explaining CENH3's tendency to bind to younger LTR.Collectively,our study describes the landscape of non-B-form DNA in the wheat genome,and sheds light on its potential role in the evolution of polyploid centromeres.
文摘目的:探讨着丝粒蛋白F(centromere protein F,CENPF)在腺样囊性癌(adenoid cystic carcinoma,ACC)发生发展中的作用和分子机制。方法:通过小干扰RNA转染敲低ACC细胞中的CENPF。通过细胞计数试剂盒(cell counting kit-8,CCK-8)、划痕实验和Transwell测定评估敲低CENPF对ACC细胞增殖、迁移、侵袭的影响;通过蛋白免疫印迹实验分析改变CENPF表达后ACC细胞中磷脂酰肌醇-3-激酶(phosphatidylinositol-3-kinase,PI3K)/丝氨酸/苏氨酸蛋白激酶(serine/threonine protein kinase,AKT)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路相关蛋白表达变化,通过CCK-8、划痕实验和Transwell测定评估敲低CENPF联合PI3K抑制剂BKM-120对ACC细胞增殖、迁移、侵袭的影响。结果:敲低ACC-M中CENPF表达后,CCK-8实验证明其增殖能力减弱;划痕实验表明其迁移能力减弱,Transwell实验表明其侵袭能力减弱,PI3K/AKT通路关键蛋白p-PI3K、p-AKT和p-mTOR蛋白表达水平下降。在下调CENPF的ACC-M中加入PI3K抑制剂,PI3K/AKT通路关键蛋白表达水平进一步下降。此外,加入PI3K抑制剂后,CENPF下调的ACC-M增殖、迁移、侵袭能力较单纯下调CENPF的ACC-M进一步减弱。结论:CENPF通过调控PI3K/AKT信号通路参与ACC进展。