ETS protein-dependent accessibility changes at the immunoglobulin mu heavy chain enhancer.
Directed accessibility mediated by antigen-receptor gene enhancers ensures developmental stage-specific activation of V(D)J recombination. Here, we used a combination of in vitro and in vivo assays to explore the mechanisms that regulate immunoglobulin mu heavy chain gene enhancer-dependent chromatin accessibility. Ets-1 or PU.1 bound to mu enhancer-containing plasmids assembled into chromatin in vitro and increased restriction enzyme access to a proximal site. In complementary analyses, expression of PU.1 in Ets-1-containing 2017 pro-T cells or NIH 3T3 cells induced sterile I mu transcripts at the IgH locus and increased accessibility of the endogenous mu enhancer to restriction endonucleases. These observations suggest that one role of PU.1 is to increase accessibility of the mu locus to initiate heavy chain gene expression.
Nikolajczyk
B S
BS
Rosenstiel Research Center and Department of Biology, Brandeis University, Waltham, Massachusetts 02454, USA.
Sanchez
J A
JA
Sen
R
R
D016475:3T3 Cells; D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D007148:Immunoglobulin mu-Chains / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D050783:Proto-Oncogene Proteins c-ets; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000276:immunology; D014981:Xenopus; D000099232:Proto-Oncogene Protein Spi-1
D002843:Chromatin; D004262:DNA Restriction Enzymes; D007143:Immunoglobulin Heavy Chains; D007148:Immunoglobulin mu-Chains; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011947:Receptors, Antigen, B-Cell; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C494042:Ets1 protein, mouse