Translational isoforms of FOG1 regulate GATA1-interacting complexes.
Erythropoietic and megakaryocytic programs are directed by the transcription factor GATA1. Friend of GATA1 (FOG1), a protein interaction partner of GATA1, is critical for GATA1 function in multiple contexts. Previous work has shown that FOG1 recruits two multi-protein complexes, the nucleosome remodeling domain (NuRD) complex and a C-terminal binding protein (CTBP)-containing complex, into association with GATA1 to mediate activation and repression of target genes. To elucidate mechanisms that might differentially regulate the association of FOG1, as well as GATA1, with these two complexes, we characterized a previously unrecognized translational isoform of FOG1. We found that an N-terminally truncated version of FOG1 is produced from an internal ATG and that this isoform, designated FOG1S, lacks the nucleosome remodeling domain-binding domain, altering the complexes with which it interacts. Both isoforms interact with the C-terminal binding protein complex, which we show also contains lysine-specific demethylase 1 (LSD1). FOG1S is preferentially excluded from the nucleus by unknown mechanisms. These data reveal two novel mechanisms for the regulation of GATA1 interaction with FOG1-dependent protein complexes through the production of two translational isoforms with differential interaction profiles and independent nuclear localization controls.
Snow
Jonathan W
JW
Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA.
Orkin
Stuart H
SH
D000818:Animals; D045744:Cell Line, Tumor; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; C494689:Gata1 protein, mouse; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; C498432:ZFPM1 protein, human; C107310:Zfpm1 protein, mouse; D056466:Histone Demethylases; C504076:KDM1a protein, mouse; C495195:KDM1A protein, human; D010089:Oxidoreductases, N-Demethylating; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex