CTCF controls expression and chromatin architecture of the human major histocompatibility complex class II locus.

Abstract:

:The major histocompatibility complex class II (MHC-II) locus includes a dense cluster of genes that function to initiate immune responses. Expression of insulator CCCTC binding factor (CTCF) was found to be required for expression of all MHC class II genes associated with antigen presentation. Ten CTCF sites that divide the MHC-II locus into apparent evolutionary domains were identified. To define the role of CTCF in mediating regulation of the MHC II genes, chromatin conformation capture assays, which provide an architectural assessment of a locus, were conducted across the MHC-II region. Depending on whether MHC-II genes and the class II transactivator (CIITA) were being expressed, two CTCF-dependent chromatin architectural states, each with multiple configurations and interactions, were observed. These states included the ability to express MHC-II gene promoter regions to interact with nearby CTCF sites and CTCF sites to interact with each other. Thus, CTCF organizes the MHC-II locus into a novel basal architecture of interacting foci and loop structures that rearranges in the presence of CIITA. Disruption of the rearranged states eradicated expression, suggesting that the formation of these structures is key to coregulation of MHC-II genes and the locus.

journal_name

Mol Cell Biol

authors

Majumder P,Boss JM

doi

10.1128/MCB.00327-10

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

4211-23

issue

17

eissn

0270-7306

issn

1098-5549

pii

MCB.00327-10

journal_volume

30

pub_type

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