title: SWI/SNF Subunits SMARCA4, SMARCD2 and DPF2 Collaborate in MLL-Rearranged Leukaemia Maintenance.
abstract: Alterations in chromatin structure caused by deregulated epigenetic mechanisms collaborate with underlying genetic lesions to promote cancer. SMARCA4/BRG1, a core component of the SWI/SNF ATP-dependent chromatin-remodelling complex, has been implicated by its mutational spectrum as exerting a tumour-suppressor function in many solid tumours; recently however, it has been reported to sustain leukaemogenic transformation in MLL-rearranged leukaemia in mice. Here we further explore the role of SMARCA4 and the two SWI/SNF subunits SMARCD2/BAF60B and DPF2/BAF45D in leukaemia. We observed the selective requirement for these proteins for leukaemic cell expansion and self-renewal in-vitro as well as in leukaemia. Gene expression profiling in human cells of each of these three factors suggests that they have overlapping functions in leukaemia. The gene expression changes induced by loss of the three proteins demonstrate that they are required for the expression of haematopoietic stem cell associated genes but in contrast to previous results obtained in mouse cells, the three proteins are not required for the expression of c-MYC regulated genes.
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.|Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
authors.forename: V Adam
authors.initials: VA
authors.lastname: Cruickshank
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.|Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Sroczynska
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.|Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
authors.forename: Aditya
authors.initials: A
authors.lastname: Sankar
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.|Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.|The Danish Stem Cell Centre (Danstem), University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyagi
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
authors.forename: Carsten Friis
authors.initials: CF
authors.lastname: Rundsten
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
authors.forename: Jens Vilstrup
authors.initials: JV
authors.lastname: Johansen
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.|Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.|The Danish Stem Cell Centre (Danstem), University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Helin
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D055785:Gene Knockdown Techniques; D015321:Gene Rearrangement; D007938:Leukemia / Q000235:genetics / Q000473:pathology*; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D022423:Myeloid Cells / Q000473:pathology; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C113581:DPF2 protein, human; C550323:DPF2 protein, mouse; D009124:Muscle Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; C491651:SMARCD2 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; C494056:Smarcd2 protein, mouse; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases