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CTCF和cohesin参与人成纤维细胞中HOXA基因簇染色质高级构象的组织

DOI: 10.1007/s11427-015-4913-5, PP. 768-776

Keywords: 人成纤维细胞,HOXA基因簇,染色质高级构象,CTCF,cohesin

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Abstract:

位于人体不同部位的成纤维细胞具有细胞特异性的HOX基因表达模式,可以作为区分不同成纤维细胞的依据之一.在个体发育的过程中,建立或维持不同HOX基因表达模式的机制始终是引人关注的问题.本实验室前期工作在NT2/D1人畸胎瘤细胞中证明了CTCF/cohesin介导的染色质高级构象在维甲酸诱导的HOXA基因共线性开启过程中发挥了重要作用.为了进一步研究原代细胞中CTCF/cohesin对HOXA基因的调控作用,本研究选取了来自体轴不同部位并且HOXA基因表达模式互补的人胚肺和包皮成纤维细胞,对HOXA基因簇中CTCF和cohesin的结合水平以及相关的染色质高级构象进行了检测.与人胚肺成纤维细胞相比,包皮成纤维细胞中的cohesin结合水平较低,相关的染色质高级构象比较“开放”,并且主要表达5'端的HOXA基因.本研究还发现CTCF结合位点CBSA56处于HOXA基因簇染色质高级构象中的核心位置,并且该位点参与的染色质相互作用在两种成纤维细胞中呈现出明显的差异,说明CBSA56是一个关键的CTCF结合位点.以上结果表明,CTCF和cohesin参与了人原代成纤维细胞中HOXA基因簇染色质高级构象的组织和HOXA基因的表达调控,并且提示细胞类型特异性的染色质高级构象与HOXA基因的空间共线性表达模式之间存在协同关系.

References

[1]  1 Rinn J L, Bondre C, Gladstone H B, et al. Anatomic demarcation by positional variation in fibroblast gene expression programs. PLoS Genet, 2006, 2: e119
[2]  2 Chang H Y, Chi J T, Dudoit S, et al. Diversity, topographic differentiation, and positional memory in human fibroblasts. Proc Natl Acad Sci USA, 2002, 99: 12877-12882
[3]  3 Wang K C, Helms J A, Chang H Y. Regeneration, repair and remembering identity: the three Rs of Hox gene expression. Trends Cell Biol, 2009, 19: 268-275
[4]  4 Duboule D. The rise and fall of Hox gene clusters. Development, 2007, 134: 2549-2560
[5]  5 Spitz F, Gonzalez F, Duboule D. A global control region defines a chromosomal regulatory landscape containing the HoxD cluster. Cell, 2003, 113: 405-417
[6]  6 Sharpe J, Nonchev S, Gould A, et al. Selectivity, sharing and competitive interactions in the regulation of Hoxb genes. EMBO J, 1998, 17: 1788-1798
[7]  7 Kmita M, Duboule D. Organizing axes in time and space; 25 years of colinear tinkering. Science, 2003, 301: 331-333
[8]  8 Kondo T, Duboule D. Breaking colinearity in the mouse HoxD complex. Cell, 1999, 97: 407-417
[9]  9 Roelen B A, de Graaff W, Forlani S, et al. Hox cluster polarity in early transcriptional availability: a high order regulatory level of clustered Hox genes in the mouse. Mech Dev, 2002, 119: 81-90
[10]  10 Fraser J, Rousseau M, Shenker S, et al. Chromatin conformation signatures of cellular differentiation. Genome Biol, 2009, 10: R37
[11]  11 Rousseau M, Crutchley J L, Miura H, et al. Hox in motion: tracking HoxA cluster conformation during differentiation. Nucleic Acids Res, 2014, 42: 1524-1540
[12]  12 Chambeyron S, Bickmore W A. Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. Genes Dev, 2004, 18: 1119-1130
[13]  13 Noordermeer D, Leleu M, Splinter E, et al. The dynamic architecture of Hox gene clusters. Science, 2011, 334: 222-225
[14]  14 Chambeyron S, Da Silva N R, Lawson K A, et al. Nuclear re-organisation of the Hoxb complex during mouse embryonic development. Development, 2005, 132: 2215-2223
[15]  15 Phillips J E, Corces V G. CTCF: master weaver of the genome. Cell, 2009, 137: 1194-1211
[16]  16 Parelho V, Hadjur S, Spivakov M, et al. Cohesins functionally associate with CTCF on mammalian chromosome arms. Cell, 2008, 132: 422-433
[17]  17 Gause M, Schaaf C A, Dorsett D. Cohesin and CTCF: cooperating to control chromosome conformation? Bioessays, 2008, 30: 715-718
[18]  18 Xu M, Zhao G N, Lv X, et al. CTCF controls HOXA cluster silencing and mediates PRC2-repressive higher-order chromatin structure in NT2/D1 cells. Mol Cell Biol, 2014, 34: 3867-3879
[19]  19 Li M, Ti D, Han W, et al. Microenvironment-induced myofibroblast-like conversion of engrafted keratinocytes. Sci China Life Sci, 2014, 57: 209-220
[20]  20 Liu X, Huang Q, Li F, et al. Enhancing the efficiency of direct reprogramming of human primary fibroblasts into dopaminergic neuron-like cells through p53 suppression. Sci China Life Sci, 2014, 57: 867-875
[21]  21 Rinn J L, Kertesz M, Wang J K, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell, 2007, 129: 1311-1323
[22]  22 Rubio E D, Reiss D J, Welcsh P L, et al. CTCF physically links cohesin to chromatin. Proc Natl Acad Sci USA, 2008, 105: 8309-8314
[23]  23 Kim Y J, Cecchini K R, Kim T H. Conserved, developmentally regulated mechanism couples chromosomal looping and heterochromatin barrier activity at the homeobox gene a locus. Proc Natl Acad Sci USA, 2011, 108: 7391-7396
[24]  24 Yusufzai T M, Felsenfeld G. The 5''-HS4 chicken beta-globin insulator is a CTCF-dependent nuclear matrix-associated element. Proc Natl Acad Sci USA, 2004, 101: 8620-8624
[25]  25 Yusufzai T M, Tagami H, Nakatani Y, et al. CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species. Mol Cell, 2004, 13: 291-298
[26]  26 Hou C, Dale R, Dean A. Cell type specificity of chromatin organization mediated by CTCF and cohesin. Proc Natl Acad Sci USA, 2010, 107: 3651-3656

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