title: Cooperative action of TIP48 and TIP49 in H2A.Z exchange catalyzed by acetylation of nucleosomal H2A.
abstract: H2A.Z is an evolutionarily conserved H2A variant that plays a key role in the regulation of chromatin transcription. To understand the molecular mechanism of H2A.Z exchange, we purified two distinct H2A.Z-interacting complexes termed the small and big complexes from a human cell line. The big complex contains most components of the SRCAP chromatin remodeling and TIP60 HAT complexes, whereas the small complex possesses only a subset of SRCAP and TIP60 subunits. Our exchange analysis revealed that both small and big complexes enhance the incorporation of H2A.Z-H2B dimer into the nucleosome. In addition, TIP60-mediated acetylation of nucleosomal H2A specifically facilitates the action of the small complex in the H2A.Z exchange reaction. Among factors present in the small complex, we determined that TIP48 and TIP49 play a major role in catalyzing H2A acetylation-induced H2A.Z exchange via their ATPase activities. Overall, our work uncovers the previously-unrecognized role of TIP48 and TIP49 in H2A.Z exchange and a novel epigenetic mechanism controlling this process.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA.
authors.forename: Jongkyu
authors.initials: J
authors.lastname: Choi
authors.forename: Kyu
authors.initials: K
authors.lastname: Heo
authors.forename: Woojin
authors.initials: W
authors.lastname: An
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002384:Catalysis; D002843:Chromatin / Q000201:enzymology; D004265:DNA Helicases / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D009707:Nucleosomes / Q000201:enzymology*; D021122:Protein Subunits / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D021122:Protein Subunits; C077020:histone H2A.F-Z; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C119652:SRCAP protein, human; C486549:RUVBL1 protein, human; C122079:RUVBL2 protein, human
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