Two mammalian MOF complexes regulate transcription activation by distinct mechanisms.
In mammals, MYST family histone acetyltransferase MOF plays important roles in transcription activation by acetylating histone H4 on K16, a prevalent mark associated with chromatin decondensation, and transcription factor p53 on K120, which is important for activation of proapoptotic genes. However, little is known about MOF regulation in higher eukaryotes. Here, we report that the acetyltransferase activity of MOF is tightly regulated in two different but evolutionarily conserved complexes, MSL and MOF-MSL1v1. Importantly, we demonstrate that while the two MOF complexes have indistinguishable activity on histone H4 K16, they differ dramatically in acetylating nonhistone substrate p53. We further demonstrate that MOF-MSL1v1 is specifically required for optimal transcription activation of p53 target genes both in vitro and in vivo. Our results support a model that these two MOF complexes regulate distinct stages of transcription activation in cooperation with other histone modifying activities.
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Xiangzhi
X
Li
Lipeng
L
Wu
Callie Ann Sprunger
CA
Corsa
Steve
S
Kunkel
Yali
Y
Dou
D000107:Acetylation; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008322:Mammals / Q000378:metabolism*; D008957:Models, Genetic; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D013379:Substrate Specificity; D015533:Transcriptional Activation / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D046912:Multiprotein Complexes; D009707:Nucleosomes; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051548:Histone Acetyltransferases; C496552:KAT8 protein, human; D008239:Lysine