ZMYM2 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着关键作用。它与多种疾病有关，例如肾脏先天性异常（其活性减弱）和癌症（其参与致癌融合蛋白事件）。 ZMYM2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 ZMYM2 在人类细胞中的功能，并证明 ZMYM2 是不同染色质结合复合物的一部分，包括已建立的 LSD1-CoREST-HDAC1 辅阻遏物复合物。我们还确定了 ADNP 和 TRIM28/KAP1 的新功能和物理相互作用。 ZMYM2-TRIM28 复合物以 SUMO 依赖性方式形成，并与抑制性染色质相关。 ZMYM2和TRIM28表现出很强的功能相似性并共同调控大量基因。然而，ZMYM2-TRIM28 结合事件与附近的个体基因调控之间没有很强的联系。相反，ZMYM2-TRIM28 似乎在 TAD 内以更具区域性定义的方式调节基因，它可以直接调节共相关的逆转录转座子表达。我们发现不同类型的 ZMYM2 结合复合物与反转录转座子的不同亚类相关联并对其进行调节，其中 ZMYM2-ADNP 复合物位于 SINE 处，ZMYM2-TRIM28 复合物位于 LTR 元件处。我们提出了一个模型，其中 ZMYM2 通过逆转录转座子调节直接发挥作用，这可能会影响局部染色质环境和相关编码基因表达。© 2023，Owen，Aguilar-Martinez，Ji 等人。

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.© 2023, Owen, Aguilar-Martinez, Ji et al.