A 220-nucleotide deletion of the intronic enhancer reveals an epigenetic hierarchy in immunoglobulin heavy chain locus activation

Tirtha Chakraborty, Thomas Perlot, Ramesh Subrahmanyam, Anant Jani, Peter H. Goff, Yu Zhang, Irina Ivanova, Frederick W. Alt, Ranjan Sen

Research output: Contribution to journalArticle

Abstract

A tissue-specific transcriptional enhancer, Eμ, has been implicated in developmentally regulated recombination and transcription of the immunoglobulin heavy chain (IgH) gene locus. We demonstrate that deleting 220 nucleotides that constitute the core Eμ results in partially active locus, characterized by reduced histone acetylation, chromatin remodeling, transcription, and recombination, whereas other hallmarks of tissue-specific locus activation, such as loss of H3K9 dimethylation or gain of H3K4 dimethylation, are less affected. These observations define Eμ-independent and Eμ-dependent phases of locus activation that reveal an unappreciated epigenetic hierarchy in tissue-specific gene expression.

Original languageEnglish (US)
Pages (from-to)1019-1027
Number of pages9
JournalJournal of Experimental Medicine
Volume206
Issue number5
DOIs
StatePublished - May 11 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Chakraborty, T., Perlot, T., Subrahmanyam, R., Jani, A., Goff, P. H., Zhang, Y., Ivanova, I., Alt, F. W., & Sen, R. (2009). A 220-nucleotide deletion of the intronic enhancer reveals an epigenetic hierarchy in immunoglobulin heavy chain locus activation. Journal of Experimental Medicine, 206(5), 1019-1027. https://doi.org/10.1084/jem.20081621