ZMYM2 controls human transposable element transcription through distinct co-regulatory complexes.
ZMYM2 controls human transposable element transcription through distinct co-regulatory complexes.
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DOI：
10.7554/elife.86669
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发表时间：
2023-11-07
期刊：
影响因子：
7.7
通讯作者：
Sharrocks AD
中科院分区：
文献类型：
--
作者：
Owen DJ;Aguilar-Martinez E;Ji Z;Li Y;Sharrocks AD
ZMYM 2是一种锌指转录调节因子，在促进和维持细胞身份方面发挥关键作用。它与几种疾病有关，如其活性降低的先天性肾脏异常和参与致癌融合蛋白事件的癌症。ZMYM 2被认为是通过促进转录抑制发挥作用，在这里，我们提供了更多的证据来支持这一指定。在这里，我们研究了ZMYM 2在人类细胞中的功能，并证明ZMYM 2是不同的染色质结合复合物的一部分，包括已建立的LSD 1-CoREST-HDAC 1辅阻遏物复合物。我们还确定了ADNP和TRIM 28/KAP 1的新功能和物理相互作用。ZMYM 2-TRIM 28复合物以SUMO依赖性方式形成，并与抑制性染色质相关。ZMYM 2和TRIM 28显示出很强的功能相似性，并且共调节大量基因。然而，ZMYM 2-TRIM 28结合事件与附近的个体基因调控之间没有强联系。相反，ZMYM 2-TRIM 28似乎在TADs内以更区域定义的方式调节基因，其中它可以直接调节共相关反转录转座子表达。我们发现不同类型的ZMYM 2结合复合物与不同的逆转录转座子亚类相关并调节它们，其中ZMYM 2-ADNP复合物位于西内斯，ZMYM 2-TRIM 28复合物位于LTR元件。我们提出了一个模型，ZMYM 2直接通过逆转录转座子调节，这可能会影响当地的染色质环境和相关的编码基因的表达。
ZMYM2 is a zinc finger transcriptional regulator that plays a key role in promoting and maintaining cell identity. It has been implicated in several diseases such as congenital anomalies of the kidney where its activity is diminished and cancer where it participates in oncogenic fusion protein events. ZMYM2 is thought to function through promoting transcriptional repression and here we provide more evidence to support this designation. Here we studied ZMYM2 function in human cells and demonstrate that ZMYM2 is part of distinct chromatin-bound complexes including the established LSD1-CoREST-HDAC1 corepressor complex. We also identify new functional and physical interactions with ADNP and TRIM28/KAP1. The ZMYM2-TRIM28 complex forms in a SUMO-dependent manner and is associated with repressive chromatin. ZMYM2 and TRIM28 show strong functional similarity and co-regulate a large number of genes. However, there are no strong links between ZMYM2-TRIM28 binding events and nearby individual gene regulation. Instead, ZMYM2-TRIM28 appears to regulate genes in a more regionally defined manner within TADs where it can directly regulate co-associated retrotransposon expression. We find that different types of ZMYM2 binding complex associate with and regulate distinct subclasses of retrotransposons, with ZMYM2-ADNP complexes at SINEs and ZMYM2-TRIM28 complexes at LTR elements. We propose a model whereby ZMYM2 acts directly through retrotransposon regulation, which may then potentially affect the local chromatin environment and associated coding gene expression.
影响因子：
14.9
作者：
Ji Z;Li Y;Liu SX;Sharrocks AD
通讯作者：
Sharrocks AD