A role of the CTCF binding site at enhancer Eα in the dynamic chromatin organization of the Tcra-Tcrd locus

Nucleic Acids Res. 2020 Sep 25;48(17):9621-9636. doi: 10.1093/nar/gkaa711.

Abstract

The regulation of T cell receptor Tcra gene rearrangement has been extensively studied. The enhancer Eα plays an essential role in Tcra rearrangement by establishing a recombination centre in the Jα array and a chromatin hub for interactions between Vα and Jα genes. But the mechanism of the Eα and its downstream CTCF binding site (here named EACBE) in dynamic chromatin regulation is unknown. The Hi-C data showed that the EACBE is located at the sub-TAD boundary which separates the Tcra-Tcrd locus and the downstream region including the Dad1 gene. The EACBE is required for long-distance regulation of the Eα on the proximal Vα genes, and its deletion impaired the Tcra rearrangement. We also noticed that the EACBE and Eα regulate the genes in the downstream sub-TAD via asymmetric chromatin extrusion. This study provides a new insight into the role of CTCF binding sites at TAD boundaries in gene regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Binding Sites
  • CCCTC-Binding Factor / genetics
  • CCCTC-Binding Factor / metabolism*
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
  • Homeodomain Proteins / genetics
  • Membrane Proteins / genetics
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Thymus Gland / cytology

Substances

  • Apoptosis Regulatory Proteins
  • CCCTC-Binding Factor
  • Chromatin
  • Ctcf protein, mouse
  • Dad1 protein, mouse
  • Homeodomain Proteins
  • Membrane Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • RAG-1 protein