The Insulator Factor CTCF Controls MHC Class II Gene Expression and is Required for the Formation of Long-distance Chromatin Interactions

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2008 Mar 19

PMID 18347100

Citations 117

Authors

Parimal Majumder

Jorge A Gomez

Brian P Chadwick

Jeremy M Boss

Affiliations

Soon will be listed here.

Abstract

Knockdown of the insulator factor CCCTC binding factor (CTCF), which binds XL9, an intergenic element located between HLA-DRB1 and HLA-DQA1, was found to diminish expression of these genes. The mechanism involved interactions between CTCF and class II transactivator (CIITA), the master regulator of major histocompatibility complex class II (MHC-II) gene expression, and the formation of long-distance chromatin loops between XL9 and the proximal promoter regions of these MHC-II genes. The interactions were inducible and dependent on the activity of CIITA, regulatory factor X, and CTCF. RNA fluorescence in situ hybridizations show that both genes can be expressed simultaneously from the same chromosome. Collectively, the results suggest a model whereby both HLA-DRB1 and HLA-DQA1 loci can interact simultaneously with XL9, and describe a new regulatory mechanism for these MHC-II genes involving the alteration of the general chromatin conformation of the region and their regulation by CTCF.

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