PMID- 27382057 OWN - NLM STAT- MEDLINE DCOM- 20170512 LR - 20210205 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 291 IP - 35 DP - 2016 Aug 26 TI - Chromatin Remodeler Recruitment during Macrophage Differentiation Facilitates Transcription Factor Binding to Enhancers in Mature Cells. PG - 18058-18071 LID - 10.1074/jbc.M116.734186 [doi] AB - We show how enhancers of macrophage-specific genes are rendered accessible in differentiating macrophages to allow their induction in mature cells in response to an appropriate stimulus. Using a lentiviral knockdown approach in primary differentiating macrophages from mouse bone marrow, we demonstrate that enhancers of Il12b and Il1a are kept relatively lowly occupied by nucleosomes and accessible through recruitment of the nucleosome remodeler BAF/PBAF. Our results using an inducible cell line that expresses an estrogen receptor fusion of the macrophage-specific transcription factor PU.1 (PUER) show that BAF/PBAF recruitment to these enhancers is a consequence of translocation of PUER to the nucleus in the presence of tamoxifen, and we speculate that remodeler recruitment may be directly mediated by PU.1. In the absence of BAF/PBAF recruitment, nucleosome occupancy at the enhancer of Il12b (and to a lesser extent at Il1a) reaches high levels in bone marrow-derived macrophages (BMDMs), and the enhancers are not fully cleared of nucleosomes upon LPS induction, resulting in impaired gene expression. Analysis of Il12b expression in single cells suggests that recruitment of the remodeler is necessary for high levels of transcription from the same promoter, and we propose that remodelers function by increasing nucleosome turnover to facilitate transcription factor over nucleosome binding in a process we have termed "remodeler-assisted competition." CI - (c) 2016 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - McAndrew, Michael J AU - McAndrew MJ AD - the Genetics Graduate Program, Michigan State University, East Lansing, Michigan 48824. AD - From the Department of Biochemistry and Molecular Biology and. FAU - Gjidoda, Alison AU - Gjidoda A AD - From the Department of Biochemistry and Molecular Biology and. FAU - Tagore, Mohita AU - Tagore M AD - the Genetics Graduate Program, Michigan State University, East Lansing, Michigan 48824. AD - From the Department of Biochemistry and Molecular Biology and. FAU - Miksanek, Tyler AU - Miksanek T AD - From the Department of Biochemistry and Molecular Biology and. FAU - Floer, Monique AU - Floer M AUID- ORCID: 0000-0001-9593-9069 AD - the Genetics Graduate Program, Michigan State University, East Lansing, Michigan 48824 floer@msu.edu. AD - From the Department of Biochemistry and Molecular Biology and. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160705 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Chromosomal Proteins, Non-Histone) RN - 0 (Nucleosomes) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Receptors, Estrogen) RN - 0 (Recombinant Fusion Proteins) RN - 0 (SWI-SNF-B chromatin-remodeling complex) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - 0 (proto-oncogene protein Spi-1) SB - IM MH - Animals MH - Cell Differentiation/*physiology MH - Chromosomal Proteins, Non-Histone/genetics/*metabolism MH - Enhancer Elements, Genetic/*physiology MH - Humans MH - Macrophages/*metabolism MH - Mice MH - Nucleosomes/genetics/metabolism MH - Proto-Oncogene Proteins/genetics/*metabolism MH - Receptors, Estrogen/genetics/*metabolism MH - Recombinant Fusion Proteins/genetics/metabolism MH - Trans-Activators/genetics/*metabolism MH - Transcription Factors/genetics/*metabolism PMC - PMC5000056 OTO - NOTNLM OT - chromatin OT - chromatin remodeler OT - chromatin remodeling OT - gene expression OT - gene regulation OT - macrophage OT - nucleosome occupancy EDAT- 2016/07/07 06:00 MHDA- 2017/05/13 06:00 PMCR- 2017/08/26 CRDT- 2016/07/07 06:00 PHST- 2016/04/21 00:00 [received] PHST- 2016/07/07 06:00 [entrez] PHST- 2016/07/07 06:00 [pubmed] PHST- 2017/05/13 06:00 [medline] PHST- 2017/08/26 00:00 [pmc-release] AID - S0021-9258(20)32171-2 [pii] AID - M116.734186 [pii] AID - 10.1074/jbc.M116.734186 [doi] PST - ppublish SO - J Biol Chem. 2016 Aug 26;291(35):18058-18071. doi: 10.1074/jbc.M116.734186. Epub 2016 Jul 5.