Cooperative action of TIP48 and TIP49 in H2A.Z exchange catalyzed by acetylation of nucleosomal H2A.

Cooperative action of TIP48 and TIP49 in H2A.Z exchange catalyzed by acetylation of nucleosomal H2A.
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DOI:
10.1093/nar/gkp660
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发表时间:
2009-10
影响因子:
14.9
通讯作者:
An W
An W
中科院分区:
生物学2区
文献类型:
--
作者:
Choi J;Heo K;An W

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H2A.Z是一种进化上保守的H2 A变体,在染色质转录调控中起关键作用。为了理解H2 A. Z交换的分子机制,我们从人细胞系中纯化了两种不同的H2 A. Z相互作用复合物,称为小复合物和大复合物。大复合物包含SRCAP染色质重塑和TIP 60 HAT复合物的大部分组分,而小复合物仅具有SRCAP和TIP 60亚基的子集。我们的交换分析表明,无论是小的和大的复合物增强掺入H2 A. Z-H2 B二聚体到核小体。此外,TIP 60介导的核小体H2 A的乙酰化特别有利于H2A.Z交换反应中小复合物的作用。在小复合物中存在的因子中,我们确定TIP 48和TIP 49通过其ATP酶活性在催化H2 A乙酰化诱导的H2A.Z交换中起主要作用。总的来说,我们的工作揭示了TIP 48和TIP 49在H2A.Z交换中以前未被认识到的作用,以及控制这一过程的一种新的表观遗传机制。
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.
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