Runx-dependent and silencer-independent repression of a maturation enhancer in the Cd4 gene

Satoshi Kojo, Nighat Yasmin, Sawako Muroi, Mari Tenno, Ichiro Taniuchi

研究成果: Contribution to journalArticle査読

5 被引用数 (Scopus)

抄録

An intronic silencer, S4, in the Cd4 gene has been shown to be responsible for the helper-lineage-specific expression of CD4; S4 requires Runx complex binding to exert its silencer function against the enhancer-mediated Cd4 activation by modulating the epigenetic state of the Cd4 gene. Here we identify a late-acting maturation enhancer. Bcl11b plays essential roles for activation of both the early-acting proximal enhancer and maturation enhancer of Cd4. Notably, Runx complexes suppress these enhancers by distinct mechanisms. Whereas repression of the proximal enhancer depends on the S4 silencer, the maturation enhancer is repressed by Runx in the absence of S4. Moreover, ThPOK, known to antagonize S4-mediated Cd4 repression, assists Runx complexes to restrain maturation enhancer activation. Distinct modes of S4 silencer action upon distinct enhancers thus unravel a pathway that restricts CD4 expression to helper-lineage cells by silencer-independent and Runx-dependent repression of maturation enhancer activity in cytotoxic-lineage cells.

本文言語英語
論文番号3593
ジャーナルNature communications
9
1
DOI
出版ステータス出版済み - 12 1 2018
外部発表はい

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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