A 220-nucleotide deletion of the intronic enhancer reveals an epigenetic hierarchy in immunoglobulin heavy chain locus activation.
A tissue-specific transcriptional enhancer, Emu, 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 Emu 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 Emu-independent and Emu-dependent phases of locus activation that reveal an unappreciated epigenetic hierarchy in tissue-specific gene expression.
Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Tirtha
T
Chakraborty
Thomas
T
Perlot
Ramesh
R
Subrahmanyam
Anant
A
Jani
Peter H
PH
Goff
Yu
Y
Zhang
Irina
I
Ivanova
Frederick W
FW
Alt
Ranjan
R
Sen
D000818:Animals; D002460:Cell Line; D003850:Deoxyribonuclease I; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000276:immunology*; D006657:Histones / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007438:Introns / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic
D006657:Histones; D007143:Immunoglobulin Heavy Chains; D003850:Deoxyribonuclease I