Mammalian cells contain two functionally distinct PBAF complexes incorporating different isoforms of PHF10 signature subunit.
The PBAF subtype of the mammalian chromatin remodeling SWI/SNF complex has wide and diverse functions in transcription regulation and development, being both transcription activator and repressor. However, a mechanism accounting for such functional diversity remains unclear. Human PHF10/BAF45a subunit of the PBAF complex plays an important role in brain development but has not been studied sufficiently. We have shown that the PHF10 gene encodes 2 types of evolutionarily conserved, ubiquitously expressed isoforms that are incorporated into the PBAF complex in a mutually exclusive manner. One isoform contains C-terminal tandem PHD fingers, which in the other isoform are replaced by the consensus sequence for phosphorylation-dependent SUMO 1 conjugation (PDSM). PBAF complexes containing different PHF10 isoforms can bind to the promoters of the same genes but produce different effects on the recruitment of Pol II to the promoter and on the level of gene transcription. In addition, it is only the PBAF with PHD-containing isoform that activates proliferation. Our study demonstrates the existence of functionally different PBAF complexes in mammalian cell. It also provides an insight into the molecular structure and role of human PHF10/BAF45a and characterizes it as an essential PBAF subunit.
Department of Eukaryote Transcription Factors; Institute of Gene Biology; Russian Academy of Sciences; Moscow, Russia; Department of Transcription Factors; Institute of Molecular Biology; Russian Academy of Sciences; Moscow, Russia.
Alexander V
AV
Brechalov
Department of Eukaryote Transcription Factors; Institute of Gene Biology; Russian Academy of Sciences; Moscow, Russia; Department of Transcription Factors; Institute of Molecular Biology; Russian Academy of Sciences; Moscow, Russia.
Sofia G
SG
Georgieva
Department of Eukaryote Transcription Factors; Institute of Gene Biology; Russian Academy of Sciences; Moscow, Russia.
Nataliya V
NV
Soshnikova
D000818:Animals; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004257:DNA Polymerase II / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D002868:Chromosomal Proteins, Non-Histone; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; C552094:PHF10 protein, human; D020033:Protein Isoforms; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D004257:DNA Polymerase II
PBAF signature subunits; PDSM motif; PHD domains; PHF10/BAF45; SWI/SNF chromatin remodeling complex; functionally distinct isoforms; sumoylation