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Tissue-specific CTCF-cohesin-mediated chromatin architecture delimits enhancer interactions and function in vivo.

Abstract：

:The genome is organized via CTCF-cohesin-binding sites, which partition chromosomes into 1-5 megabase (Mb) topologically associated domains (TADs), and further into smaller sub-domains (sub-TADs). Here we examined in vivo an ∼80 kb sub-TAD, containing the mouse α-globin gene cluster, lying within a ∼1 Mb TAD. We find that the sub-TAD is flanked by predominantly convergent CTCF-cohesin sites that are ubiquitously bound by CTCF but only interact during erythropoiesis, defining a self-interacting erythroid compartment. Whereas the α-globin regulatory elements normally act solely on promoters downstream of the enhancers, removal of a conserved upstream CTCF-cohesin boundary extends the sub-TAD to adjacent upstream CTCF-cohesin-binding sites. The α-globin enhancers now interact with the flanking chromatin, upregulating expression of genes within this extended sub-TAD. Rather than acting solely as a barrier to chromatin modification, CTCF-cohesin boundaries in this sub-TAD delimit the region of chromatin to which enhancers have access and within which they interact with receptive promoters.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Hanssen LLP,Kassouf MT,Oudelaar AM,Biggs D,Preece C,Downes DJ,Gosden M,Sharpe JA,Sloane-Stanley JA,Hughes JR,Davies B,Higgs DR

doi

10.1038/ncb3573

subject

Has Abstract

pub_date

2017-08-01 00:00:00

pages

952-961

issue

8

eissn

1465-7392

issn

1476-4679

pii

ncb3573

journal_volume

19

pub_type

杂志文章

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