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.
Chakraborty
Tirtha
T
Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Perlot
Thomas
T
Subrahmanyam
Ramesh
R
Jani
Anant
A
Goff
Peter H
PH
Zhang
Yu
Y
Ivanova
Irina
I
Alt
Frederick W
FW
Sen
Ranjan
R
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