CTCF Controls Expression and Chromatin Architecture of the Human Major Histocompatibility Complex Class II Locus

• Type of Material: Article
• Authors: Parimal Majumder, Emory University; Jeremy Boss, Emory University
• Language: English
• Date: 2010-09
• Publisher: American Society for Microbiology (ASM)
• Publication Version: Final Published Version
• Copyright Statement: © 2010, American Society for Microbiology
• Final Published Version (URL): http://mcb.asm.org/content/30/17/4211
• Title of Journal or Parent Work: Molecular and Cellular Biology
• Volume: 30
• Issue: 17
• Start Page: 4211
• End Page: 4223
• Grant/Funding Information: This work was supported by Public Health Service grant GM47310 from the National Institute of General Medical Sciences.
• Research Categories: Biology, Molecular; Biology, Microbiology

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.