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

Publication ,  Journal Article
Hao, B; Naik, AK; Watanabe, A; Tanaka, H; Chen, L; Richards, HW; Kondo, M; Taniuchi, I; Kohwi, Y; Kohwi-Shigematsu, T; Krangel, MS
Published in: J Exp Med
May 4, 2015

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.

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Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

May 4, 2015

Volume

212

Issue

5

Start / End Page

809 / 824

Location

United States

Related Subject Headings

  • Thymocytes
  • Response Elements
  • Mice, Knockout
  • Mice
  • Matrix Attachment Region Binding Proteins
  • Immunology
  • Homeodomain Proteins
  • Gene Expression Regulation
  • DNA-Binding Proteins
  • Chromatin
 

Citation

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Hao, B., Naik, A. K., Watanabe, A., Tanaka, H., Chen, L., Richards, H. W., … Krangel, M. S. (2015). An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development. J Exp Med, 212(5), 809–824. https://doi.org/10.1084/jem.20142207
Hao, Bingtao, Abani Kanta Naik, Akiko Watanabe, Hirokazu Tanaka, Liang Chen, Hunter W. Richards, Motonari Kondo, et al. “An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development.J Exp Med 212, no. 5 (May 4, 2015): 809–24. https://doi.org/10.1084/jem.20142207.
Hao B, Naik AK, Watanabe A, Tanaka H, Chen L, Richards HW, et al. An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development. J Exp Med. 2015 May 4;212(5):809–24.
Hao, Bingtao, et al. “An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development.J Exp Med, vol. 212, no. 5, May 2015, pp. 809–24. Pubmed, doi:10.1084/jem.20142207.
Hao B, Naik AK, Watanabe A, Tanaka H, Chen L, Richards HW, Kondo M, Taniuchi I, Kohwi Y, Kohwi-Shigematsu T, Krangel MS. An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development. J Exp Med. 2015 May 4;212(5):809–824.

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

May 4, 2015

Volume

212

Issue

5

Start / End Page

809 / 824

Location

United States

Related Subject Headings

  • Thymocytes
  • Response Elements
  • Mice, Knockout
  • Mice
  • Matrix Attachment Region Binding Proteins
  • Immunology
  • Homeodomain Proteins
  • Gene Expression Regulation
  • DNA-Binding Proteins
  • Chromatin