title: NuRD mediates activating and repressive functions of GATA-1 and FOG-1 during blood development.
abstract: GATA transcription factors interact with FOG proteins to regulate tissue development by activating and repressing transcription. FOG-1 (ZFPM1), a co-factor for the haematopoietic factor GATA-1, binds to the NuRD co-repressor complex through a conserved N-terminal motif. Surprisingly, we detected NuRD components at both repressed and active GATA-1/FOG-1 target genes in vivo. In addition, while NuRD is required for transcriptional repression in certain contexts, we show a direct requirement of NuRD also for FOG-1-dependent transcriptional activation. Mice in which the FOG-1/NuRD interaction is disrupted display defects similar to germline mutations in the Gata1 and Fog1 genes, including anaemia and macrothrombocytopaenia. Gene expression analysis in primary mutant erythroid cells and megakaryocytes (MKs) revealed an essential function for NuRD during both the repression and activation of select GATA-1/FOG-1 target genes. These results show that NuRD is a critical co-factor for FOG-1 and underscore the versatile use of NuRD by lineage-specific transcription factors to activate and repress gene transcription in the appropriate cellular and genetic context.
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Annarita
authors.initials: A
authors.lastname: Miccio
authors.forename: Yuhuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Hong
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Gregory
authors.forename: Hongxin
authors.initials: H
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Yu
authors.forename: John K
authors.initials: JK
authors.lastname: Choi
authors.forename: Suresh
authors.initials: S
authors.lastname: Shelat
authors.forename: Wei
authors.initials: W
authors.lastname: Tong
authors.forename: Mortimer
authors.initials: M
authors.lastname: Poncz
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Blobel
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D006410:Hematopoiesis; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; C107310:Zfpm1 protein, mouse; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex