An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development.

Published

Journal Article

Rag1 and Rag2 gene expression in CD4(+)CD8(+) double-positive (DP) thymocytes depends on the activity of a distant anti-silencer element (ASE) that counteracts the activity of an intergenic silencer. However, the mechanistic basis for ASE activity is unknown. Here, we show that the ASE physically interacts with the distant Rag1 and Rag2 gene promoters in DP thymocytes, bringing the two promoters together to form an active chromatin hub. Moreover, we show that the ASE functions as a classical enhancer that can potently activate these promoters in the absence of the silencer or other locus elements. In thymocytes lacking the chromatin organizer SATB1, we identified a partial defect in Tcra gene rearrangement that was associated with reduced expression of Rag1 and Rag2 at the DP stage. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters. Our results provide a novel framework for understanding ASE function and demonstrate a novel role for SATB1 as a regulator of Rag locus organization and gene expression in DP thymocytes.

Full Text

Duke Authors

Cited Authors

  • Hao, B; Naik, AK; Watanabe, A; Tanaka, H; Chen, L; Richards, HW; Kondo, M; Taniuchi, I; Kohwi, Y; Kohwi-Shigematsu, T; Krangel, MS

Published Date

  • May 4, 2015

Published In

Volume / Issue

  • 212 / 5

Start / End Page

  • 809 - 824

PubMed ID

  • 25847946

Pubmed Central ID

  • 25847946

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

Digital Object Identifier (DOI)

  • 10.1084/jem.20142207

Language

  • eng

Conference Location

  • United States