title: Histone acetyltransferase p300 acetylates Pax5 and strongly enhances Pax5-mediated transcriptional activity.
abstract: Pax5/B cell lineage specific activator protein (BSAP) is a B lineage-specific regulator that controls the B lineage-specific gene expression program and immunoglobulin gene V(H) to DJ(H) recombination. Despite extensive studies on its multiple functions, little is known about how the activity of Pax5 is regulated. Here, we show that co-expression of histone acetyltransferase E1A binding protein p300 dramatically enhances Pax5-mediated transcriptional activation. The p300-mediated enhancement is dependent on its intrinsic histone acetyltransferase activity. Moreover, p300 interacts with the C terminus of Pax5 and acetylates multiple lysine residues within the paired box DNA binding domain of Pax5. Mutations of lysine residues 67 and 87/89 to alanine within Pax5 abolish p300-mediated enhancement of Pax5-induced Luc-CD19 reporter expression in HEK293 cells and prevent Pax5 to activate endogenous Cd19 and Blnk expression in Pax5(-/-) murine pro B cells. These results uncover a novel level of regulation of Pax5 function by p300-mediated acetylation.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Ti
authors.initials: T
authors.lastname: He
authors.forename: Sang Yong
authors.initials: SY
authors.lastname: Hong
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.forename: Weihua
authors.initials: W
authors.lastname: Xue
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yu
authors.forename: Hyoung
authors.initials: H
authors.lastname: Kwon
authors.forename: Marion
authors.initials: M
authors.lastname: Kirk
authors.forename: Shi-jian
authors.initials: SJ
authors.lastname: Ding
authors.forename: Kaihong
authors.initials: K
authors.lastname: Su
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018941:Antigens, CD19 / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology; D006801:Humans; D008239:Lysine / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D051757:PAX5 Transcription Factor / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D050880:p300-CBP Transcription Factors / Q000378:metabolism*
chemical_list: D018941:Antigens, CD19; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; C497282:Pax5 protein, mouse; D050880:p300-CBP Transcription Factors; D008239:Lysine