B cell differentiation is associated with reprogramming the CTCF-dependent chromatin architecture of the murine MHC-II locus1
The transcriptional insulator CCCTC binding factor (CTCF) 2 was shown previously to be critical for human MHC class II gene expression. Whether the mechanisms used by CTCF in humans was similar to that of the mouse and whether the three-dimensional chromatin architecture created was specific to B ce...
Saved in:
Published in | The Journal of immunology (1950) Vol. 192; no. 8; pp. 3925 - 3935 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
14.03.2014
|
Online Access | Get full text |
Cover
Loading…
Summary: | The transcriptional insulator CCCTC binding factor (CTCF)
2
was shown previously to be critical for human MHC class II gene expression. Whether the mechanisms used by CTCF in humans was similar to that of the mouse and whether the three-dimensional chromatin architecture created was specific to B cells was not defined. Genome-wide CTCF occupancy was defined for murine B cells and LPS-derived plasmablasts by ChIP-seq. 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 class II genes as part of the cell fate commitment of plasma cells. |
---|---|
Bibliography: | Current Address: The Scripps Research Institute, Department of Immunology and Microbial Science, 10550 North Torrey Pines Rd. IMM-22, La Jolla, CA 92037 |
ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.1303205 |