USP10 deubiquitylates the histone variant H2A.Z and both are required for androgen receptor-mediated gene activation.
USP10 deubiquitylates the histone variant H2A.Z and both are required for androgen receptor-mediated gene activation.
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DOI：
10.1093/nar/gkq1352
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发表时间：
2011-05
影响因子：
14.9
通讯作者：
Cheung P
中科院分区：
文献类型：
--
作者：
Draker R;Sarcinella E;Cheung P
H2A.Z是H2 A的一种变体，存在于酵母和高等真核生物中诱导基因的启动子上。然而，它在转录调控中的作用是复杂的，因为据报道它既作为抑制剂又作为激活剂。我们先前已经发现H2A.Z的单泛素化与转录沉默有关。在这里，我们提供了新的证据连接H2A.Z去泛素化转录激活。我们发现H2A.Z和泛素特异性蛋白酶10（USP 10）都是雄激素受体（AR）调节的PSA和KLK 3基因转录激活所必需的。USP 10在体外和体内直接去泛素化H2A.Z，降低前列腺癌细胞中USP 10的表达导致单泛素化H2A.Z（H2A.Zub1）的稳态水平升高。此外，USP 10的敲除消除了AR调节基因处的染色质蛋白的去泛素化。最后，通过连续ChIP检测，我们发现H2A.Zub1在PSA和KLK 3调控区富集，H2A.Zub1的缺失与这些基因的转录激活相关。总之，这些数据为H2A.Z泛素化/去泛素化和USP 10在AR调节的基因表达中的功能提供了新的见解。
H2A.Z, a variant of H2A, is found at the promoters of inducible genes in both yeast and higher eukaryotes. However, its role in transcriptional regulation is complex since it has been reported to function both as a repressor and activator. We have previously found that mono-ubiquitylation of H2A.Z is linked to transcriptional silencing. Here, we provide new evidence linking H2A.Z deubiquitylation to transcription activation. We found that H2A.Z and ubiquitin-specific protease 10 (USP10) are each required for transcriptional activation of the androgen receptor (AR)-regulated PSA and KLK3 genes. USP10 directly deubiquitylates H2A.Z in vitro and in vivo, and reducing USP10 expression in prostate cancer cells results in elevated steady-state levels of mono-ubiquitylated H2A.Z (H2A.Zub1). Moreover, knockdown of USP10 ablates hormone-induced deubiquitylation of chromatin proteins at the AR-regulated genes. Finally, by sequential ChIP assays, we found that H2A.Zub1 is enriched at the PSA and KLK3 regulatory regions, and loss of H2A.Zub1 is associated with transcriptional activation of these genes. Together, these data provide novel insights into how H2A.Z ubiquitylation/deubiquitylation and USP10 function in AR-regulated gene expression.
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过乙酰化形式的替换组蛋白H2A.Z是鸡肉中活性基因的特征。
影响因子：
14.9
作者：
Bruce K;Myers FA;Mantouvalou E;Lefevre P;Greaves I;Bonifer C;Tremethick DJ;Thorne AW;Crane-Robinson C
通讯作者：
Crane-Robinson C
影响因子：
3.7
作者：
de Jonge HJ;Fehrmann RS;de Bont ES;Hofstra RM;Gerbens F;Kamps WA;de Vries EG;van der Zee AG;te Meerman GJ;ter Elst A
通讯作者：
ter Elst A
影响因子：
5.3
作者：
Adam, M;Robert, F;Gaudreau, L
通讯作者：
Gaudreau, L
影响因子：
10.5
作者：
Gevry, Nicolas;Hardy, Sara;Gaudreau, Luc
通讯作者：
Gaudreau, Luc
影响因子：
4.8
作者：
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通讯作者：
Ausió, J