A far downstream enhancer for murine Bcl11b controls its T-cell specific expression

Long Li, Jingli A. Zhang, Marei Dose, Hao Yuan Kueh, Ruzbeh Mosadeghi, Fotini Gounari, Ellen V. Rothenberg

Research output: Contribution to journalArticlepeer-review


Bcl11b is a T-cell specific gene in hematopoiesis that begins expression during T-lineage commitment and is required for this process. Aberrant expression of BCL11B or protooncogene translocation to the vicinity of BCL11B can be a contributing factor in human T-ALL. To identify the mechanism that controls its distinctive T-lineage expression, we corrected the identified Bcl11b transcription start site and mapped a cell-type-specific differentially methylated region bracketing the Bcl11b promoter. We identified a 1.9-kb region 850 kb downstream of Bcl11b, "Major Peak," distinguished by its dynamic histone marking pattern in development that mirrors the pattern at the Bcl11b promoter. Looping interactions between promoter-proximal elements including the differentially methylated region and downstream elements in the Major Peak are required to recapitulate the T-cell specific expression of Bcl11b in stable reporter assays. Functional dissection of the Major Peak sequence showed distinct subregions, in which TCF-1 sites and a conserved element were required for T-lineage-specific activation and silencing in non-T cells. A bacterial artificial chromosome encompassing the full Bcl11b gene still required the addition of the Major Peak to exhibit T-cell specific expression. Thus, promoter-proximal and Major Peak sequences are cis-regulatory elements that interact over 850 kb to control expression of Bcl11b in hematopoietic cells.

Original languageEnglish (US)
Pages (from-to)902-911
Number of pages10
Issue number6
StatePublished - Aug 8 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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