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PDBsum entry 4qut
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Signaling protein
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PDB id
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4qut
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References listed in PDB file
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Key reference
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Title
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Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
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Authors
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Y.Morozumi,
F.Boussouar,
M.Tan,
A.Chaikuad,
M.Jamshidikia,
G.Colak,
H.He,
L.Nie,
C.Petosa,
M.De dieuleveult,
S.Curtet,
A.L.Vitte,
C.Rabatel,
A.Debernardi,
F.L.Cosset,
E.Verhoeyen,
A.Emadali,
N.Schweifer,
D.Gianni,
M.Gut,
P.Guardiola,
S.Rousseaux,
M.Gérard,
S.Knapp,
Y.Zhao,
S.Khochbin.
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Ref.
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J Mol Cell Biol, 2016,
8,
349-362.
[DOI no: ]
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PubMed id
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Abstract
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Although the conserved AAA ATPase and bromodomain factor, ATAD2, has been
described as a transcriptional co-activator upregulated in many cancers, its
function remains poorly understood. Here, using a combination of ChIP-seq,
ChIP-proteomics, and RNA-seq experiments in embryonic stem cells where Atad2 is
normally highly expressed, we found that Atad2 is an abundant nucleosome-bound
protein present on active genes, associated with chromatin remodelling, DNA
replication, and DNA repair factors. A structural analysis of its bromodomain
and subsequent investigations demonstrate that histone acetylation guides ATAD2
to chromatin, resulting in an overall increase of chromatin accessibility and
histone dynamics, which is required for the proper activity of the highly
expressed gene fraction of the genome. While in exponentially growing cells
Atad2 appears dispensable for cell growth, in differentiating ES cells Atad2
becomes critical in sustaining specific gene expression programmes, controlling
proliferation and differentiation. Altogether, this work defines Atad2 as a
facilitator of general chromatin-templated activities such as transcription.
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