Exploring CTCF and cohesin related chromatin architecture at HOXA gene cluster in primary human fibroblasts  

作　　者：WANG Xing XU Miao ZHAO GuangNian LIU GuoYou HAO DeLong LV Xiang LIU DePei 

机构地区：[1]State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences & Peking Union Medical College

出　　处：《Science China(Life Sciences)》2015年第9期860-866,共7页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(31030026);the National Basic Research Program(2011CB-965203);the PUMC Youth funds(3332013138)

摘　　要：Spatial expression patterns of homeobox （HOX） genes delineate positional identity of primary fibroblasts from different topo- graphic sites. The molecular mechanism underlying the establishing or maintaining of HOX gene expression pattern remains an attractive developmental issue to be addressed. Our previous work suggested a critical role of CTCF/cobesin-mediated high- er-order chromatin structure in RA-induced HOXA activation in human teratocarcinoma NT2/D1 cells. This study investigated the recruitment of CTCF and cohesin, and the higher-order chromatin structure of the HOXA locus in fetal lung and adult foreskin fibroblasts, which display complementary HOXA gene expression patterns. Chromatin contacts between the CTCF-binding sites were observed with lower frequency in human foreskin fibroblasts. This observation is consistent with the lower level of cohesin recruitment and 5＇ HOXA gene expression in the same cells. We also showed that CTCF-binding site A56 （CBSA56） related chromatin structures exhibit the most notable changes in between the two types of cell, and hence may stand for one of the key CTCF-binding sites for cell-type specific chromatin structure organization. Together, these results im- ply that CTCF/cohesin coordinates HOXA cluster higher-order chromatin structure and expression during development, and provide insight into the relationship between cell-type specific chromatin organization and the spatial collinearity.Spatial expression patterns of homeobox(HOX) genes delineate positional identity of primary fibroblasts from different topographic sites. The molecular mechanism underlying the establishing or maintaining of HOX gene expression pattern remains an attractive developmental issue to be addressed. Our previous work suggested a critical role of CTCF/cohesin-mediated higher-order chromatin structure in RA-induced HOXA activation in human teratocarcinoma NT2/D1 cells. This study investigated the recruitment of CTCF and cohesin, and the higher-order chromatin structure of the HOXA locus in fetal lung and adult foreskin fibroblasts, which display complementary HOXA gene expression patterns. Chromatin contacts between the CTCF-binding sites were observed with lower frequency in human foreskin fibroblasts. This observation is consistent with the lower level of cohesin recruitment and 5′ HOXA gene expression in the same cells. We also showed that CTCF-binding site A56(CBSA56) related chromatin structures exhibit the most notable changes in between the two types of cell, and hence may stand for one of the key CTCF-binding sites for cell-type specific chromatin structure organization. Together, these results imply that CTCF/cohesin coordinates HOXA cluster higher-order chromatin structure and expression during development, and provide insight into the relationship between cell-type specific chromatin organization and the spatial collinearity.

关 键 词：human fibroblasts HOXA cluster higher-order chromatin structure CTCF COHESION 

分 类 号：R394[医药卫生—医学遗传学]