NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1
NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1
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DOI：
10.1016/j.cell.2004.11.002
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发表时间：
2004-12-17
期刊：
影响因子：
64.5
通讯作者：
Kraus, WL
中科院分区：
文献类型：
--
作者：
Kim, MY;Mauro, S;Kraus, WL
PARP-1是一个蛋白质家族中表达最丰富的成员，该家族催化ADP核糖单位从NAD（+）转移到靶蛋白。在此，我们描述了以前未表征的核小体结合特性的PARP-1，促进形成紧凑的，转录抑制的染色质结构。PARP-1以特异性方式与核小体结合，并通过NAD（+）依赖性自修饰调节染色质结构，而不改变核心历史或促进核小体的解体。PARP-1的自修饰活性受到核小体的强烈刺激，导致PARP-1从染色质中释放。PARP-1的NAD+依赖性活性可被PARG（一种聚腺苷三磷酸核糖）糖水解酶）逆转，并被ATP抑制。在体内，PARP-1掺入与转录抑制的染色质结构域相关，这些结构域在空间上不同于组蛋白H1抑制的结构域和活跃转录的区域。因此，PARP-1通过其内在的酶活性既作为染色质的结构组分又作为染色质结构的调节剂发挥作用。
PARP-1 is the most abundantly expressed member of a family of proteins that catalyze the transfer of ADPribose units from NAD(+) to target proteins. Herein, we describe previously uncharacterized nucleosome binding properties of PARP-1 that promote the formation of compact, transcriptionally repressed chromatin structures. PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD(+)-dependent automodification, without modifying core histories or promoting the disassembly of nucleosomes. The automodification activity of PARP-1 is potently stimulated by nucleosomes, causing the release of PARP-1 from chromatin. The NAD+-dependent activities of PARP-1 are reversed by PARG, a poly(ADPribose) glycohydrolase, and are inhibited by ATP. In vivo, PARP-1 incorporation is associated with transcriptionally repressed chromatin domains that are spatially distinct from both histone H1-repressed domains and actively transcribed regions. Thus, PARP-1 functions both as a structural component of chromatin and a modulator of chromatin structure through its intrinsic enzymatic activity.