title: The SWI/SNF chromatin remodelling complex is required for maintenance of lineage specific enhancers.
abstract: Genes encoding subunits of SWI/SNF (BAF) chromatin remodelling complexes are collectively altered in over 20% of human malignancies, but the mechanisms by which these complexes alter chromatin to modulate transcription and cell fate are poorly understood. Utilizing mouse embryonic fibroblast and cancer cell line models, here we show via ChIP-seq and biochemical assays that SWI/SNF complexes are preferentially targeted to distal lineage specific enhancers and interact with p300 to modulate histone H3 lysine 27 acetylation. We identify a greater requirement for SWI/SNF at typical enhancers than at most super-enhancers and at enhancers in untranscribed regions than in transcribed regions. Our data further demonstrate that SWI/SNF-dependent distal enhancers are essential for controlling expression of genes linked to developmental processes. Our findings thus establish SWI/SNF complexes as regulators of the enhancer landscape and provide insight into the roles of SWI/SNF in cellular fate control.
authors.affiliation: Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Burak H
authors.initials: BH
authors.lastname: Alver
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02215, USA.|Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Kimberly H
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02215, USA.|Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02215, USA.|Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02215, USA.|Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Haley E
authors.initials: HE
authors.lastname: Manchester
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02215, USA.|Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Weishan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02215, USA.|Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Haswell
authors.affiliation: Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Peter J
authors.identifier: 0000-0001-9378-960X
authors.initials: PJ
authors.lastname: Park
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02215, USA.|Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02215, USA.|Comprehensive Cancer Center and Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: Charles W M
authors.initials: CW
authors.lastname: Roberts
mesh_terms: D000107:Acetylation; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D008239:Lysine