RRC ID 48758
Author Rawat P, Jalan M, Sadhu A, Kanaujia A, Srivastava M.
Title Chromatin Domain Organization of the TCRb Locus and Its Perturbation by Ectopic CTCF Binding.
Journal Mol Cell Biol
Abstract CTCF-mediated chromatin interactions influence organization and function of mammalian genome in diverse ways. We analyzed the interactions among CTCF binding sites (CBS) at the murine TCRb locus to discern the role of CTCF-mediated interactions in the regulation of transcription and VDJ recombination. Chromosome conformation capture analysis revealed thymocyte-specific long-range intrachromosomal interactions among various CBS across the locus that were relevant for defining the limit of the enhancer Eb-regulated recombination center (RC) and for facilitating the spatial proximity of TCRb variable (V) gene segments to the RC. Ectopic CTCF binding in the RC region, effected via genetic manipulation, altered CBS-directed chromatin loops, interfered with RC establishment, and reduced the spatial proximity of the RC with Trbv segments. Changes in chromatin loop organization by ectopic CTCF binding were relatively modest but influenced transcription and VDJ recombination dramatically. Besides revealing the importance of CTCF-mediated chromatin organization for TCRb regulation, the observed chromatin loops were consistent with the emerging idea that CBS orientations influence chromatin loop organization and underscored the importance of CBS orientations for defining chromatin architecture that supports VDJ recombination. Further, our study suggests that in addition to mediating long-range chromatin interactions, CTCF influences intricate configuration of chromatin loops that govern functional interactions between elements.
Volume 37(9)
Published 2017-5-1
DOI 10.1128/MCB.00557-16
PII MCB.00557-16
PMID 28137913
PMC PMC5394274
MeSH Animals Binding Sites / immunology CCCTC-Binding Factor Cells, Cultured Chromatin / metabolism* Chromatin Assembly and Disassembly / genetics* Enhancer Elements, Genetic / genetics Genome / genetics Mice Mice, Inbred C57BL Mice, Knockout Receptors, Antigen, T-Cell, alpha-beta / genetics* Regulatory Elements, Transcriptional / genetics Repressor Proteins / genetics Repressor Proteins / metabolism* V(D)J Recombination / genetics*
IF 3.611
Times Cited 5
DNA material MSM/Ms Mouse BAC (RDB04214) MSMG01-426I12