The double-histone-acetyltransferase complex ATAC is essential for mammalian development.
Acetylation of the histone tails, catalyzed by histone acetyltransferases (HATs), is a well-studied process that contributes to transcriptionally active chromatin states. Here we report the characterization of a novel mammalian HAT complex, which contains the two acetyltransferases GCN5 and ATAC2 as well as other proteins linked to chromatin metabolism. This multisubunit complex has a similar but distinct subunit composition to that of the Drosophila ADA2A-containing complex (ATAC). Recombinant ATAC2 has a weak HAT activity directed to histone H4. Moreover, depletion of ATAC2 results in the disassembly of the complex, indicating that ATAC2 not only carries out an enzymatic function but also plays an architectural role in the stability of mammalian ATAC. By targeted disruption of the Atac2 locus in mice, we demonstrate for the first time the essential role of the ATAC complex in mammalian development, histone acetylation, cell cycle progression, and prevention of apoptosis during embryogenesis.
Guelman
Sebastián
S
Department of Pathology, Genentech Inc., 1 DNA Way MS 72B, South San Francisco, CA 94080, USA.
Kozuka
Kenji
K
Mao
Yifan
Y
Pham
Victoria
V
Solloway
Mark J
MJ
Wang
John
J
Wu
Jiansheng
J
Lill
Jennie R
JR
Zha
Jiping
J
D000107:Acetylation; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D047108:Embryonic Development; D048788:Growth and Development; D051548:Histone Acetyltransferases / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000502:physiology*; D050880:p300-CBP Transcription Factors / Q000502:physiology; D000099224:p300-CBP-Associated Factor
D051548:Histone Acetyltransferases; D006657:Histones; D009097:Multienzyme Complexes; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor