title: B cell differentiation is associated with reprogramming the CCCTC binding factor-dependent chromatin architecture of the murine MHC class II locus.
abstract: The transcriptional insulator CCCTC binding factor (CTCF) was shown previously to be critical for human MHC class II (MHC-II) gene expression. Whether the mechanisms used by CTCF in humans were similar to that of the mouse and whether the three-dimensional chromatin architecture created was specific to B cells were not defined. Genome-wide CTCF occupancy was defined for murine B cells and LPS-derived plasmablasts by chromatin immunoprecipitation sequencing. Fifteen CTCF sites within the murine MHC-II locus were associated with high CTCF binding in B cells. Only one-third of these sites displayed significant CTCF occupancy in plasmablasts. CTCF was required for maximal MHC-II gene expression in mouse B cells. In B cells, a subset of the CTCF regions interacted with each other, creating a three-dimensional architecture for the locus. Additional interactions occurred between MHC-II promoters and the CTCF sites. In contrast, a novel configuration occurred in plasma cells, which do not express MHC-II genes. Ectopic CIITA expression in plasma cells to induce MHC-II expression resulted in high levels of MHC-II proteins, but did not alter the plasma cell architecture completely. These data suggest that reorganizing the three-dimensional chromatin architecture is an epigenetic mechanism that accompanies the silencing of MHC-II genes as part of the cell fate commitment of plasma cells.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: Parimal
authors.initials: P
authors.lastname: Majumder
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Scharer
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Choi
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Boss
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002454:Cell Differentiation; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006183:H-2 Antigens / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D059372:Nucleotide Motifs; D010950:Plasma Cells / Q000166:cytology / Q000378:metabolism; D056510:Position-Specific Scoring Matrices; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; C000619698:Ctcf protein, mouse; D006183:H-2 Antigens; D012097:Repressor Proteins