title: Targeted chromatin profiling reveals novel enhancers in Ig H and Ig L chain Loci.
abstract: The assembly and expression of mouse Ag receptor genes are controlled by a collection of cis-acting regulatory elements, including transcriptional promoters and enhancers. Although many powerful enhancers have been identified for Ig (Ig) and TCR (Tcr) loci, it remained unclear whether additional regulatory elements remain undiscovered. In this study, we use chromatin profiling of pro-B cells to define 38 epigenetic states in mouse Ag receptor loci, each of which reflects a distinct regulatory potential. One of these chromatin states corresponds to known transcriptional enhancers and identifies a new set of candidate elements in all three Ig loci. Four of the candidates were subjected to functional assays, and all four exhibit enhancer activity in B but not in T lineage cells. The new regulatory elements identified by focused chromatin profiling most likely have important functions in the creation, refinement, and expression of Ig repertoires.
authors.affiliation: Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Predeus
authors.forename: Suhasni
authors.initials: S
authors.lastname: Gopalakrishnan
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Feeney
authors.forename: Eugene M
authors.initials: EM
authors.lastname: Oltz
authors.forename: Maxim N
authors.initials: MN
authors.lastname: Artyomov
mesh_terms: D000107:Acetylation; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D019070:Cell Lineage; D002843:Chromatin / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000172:deficiency; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D006657:Histones / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D038041:Lymphopoiesis; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D054420:Pre-B Cell Receptors / Q000235:genetics; D011499:Protein Processing, Post-Translational; D011947:Receptors, Antigen, B-Cell / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D054420:Pre-B Cell Receptors; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; D014157:Transcription Factors