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

Abstract

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.human fibroblasts, HOXA cluster, higher-order chromatin structure, CTCF, cohesion Citation:Wang X, Xu M, Zhao GN, Liu GY, Hao DL, Lv X, Liu DP. Exploring CTCF and cohesin related chromatin architecture at HOXA gene cluster in primary human fibroblasts. Sci China Life Sci, 2015, 58: 860 -866,

Nup93 and CTCF co-modulate spatiotemporal dynamics and function of the HOXA gene cluster during differentiation

“…The temporal and collinear expression of HOXA genes is essential for normal development and differentiation (27,55,65). CTCF functions as an organizer of chromatin loops of the HOXA gene cluster which facilitates the spatiotemporal control of HOXA gene expression during differentiation (27,55,65,66). However, the mechanism underlying the regulated control of HOXA gene expression during differentiation is unclear.…”

Suv4-20h2 protects against influenza virus infection by suppression of chromatin loop formation

“…This is controlled by factors that regulate cohesin loading (e.g., NIPBL and MAU2) ( Schwarzer et al., 2017 ) and unloading (e.g., WAPL and its binding partner PDS5) ( Busslinger et al., 2017 ) ( Haarhuis et al., 2017 ). Recent chromatin conformation capture (3C)-based techniques including 4C-seq revealed cohesin-mediated CTCF loop formation in various loci, including those of the immunoglobulin ( Degner et al., 2009 ), β-globin ( Hou et al., 2010 ), interferon gamma ( Hadjur et al., 2009 ), IGF2-H19 ( Nativio et al., 2009 ; Wendt et al., 2008 ) and HOXA ( Wang et al., 2015 ) genes.…”