The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20081621
The Journal of Experimental Medicine, Vol. 206, No. 5, 1019-1027
The Rockefeller University Press, 0022-1007 $30.00
© Chakraborty et al.
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BRIEF DEFINITIVE REPORT

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

Tirtha Chakraborty1, Thomas Perlot2,3, Ramesh Subrahmanyam1, Anant Jani4, Peter H. Goff2, Yu Zhang2, Irina Ivanova1, Frederick W. Alt2, and Ranjan Sen1

1 Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224
2 The Howard Hughes Medical Institute, The Children’s Hospital, Immune Disease Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115
3 University of Vienna, A-1010 Vienna, Austria
4 Immunology Program, Yale University Medical School, New Haven, CT 06510

CORRESPONDENCE Ranjan Sen: rs465z{at}nih.gov

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.

T. Chakraborty, T. Perlot, and R. Subrahmanyam contributed equally to this paper.

T. Chakraborty's present address is Immune Disease Institute, Harvard Medical School, Boston, MA 02115.


This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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