PDF(Pubmed)
Abstract：
Long interspersed nuclear elements (LINEs) play essential roles in shaping chromatin states, while the factors that cooperate with LINEs and their roles in higher-order chromatin organization remain poorly understood. Here, we show that MATR3, a nuclear matrix protein, interplays with antisense LINE1 (AS L1) RNAs to form a meshwork via phase separation, providing a dynamic platform for chromatin spatial organization. MATR3 and AS L1 RNAs affect the nuclear localization of each other. After MATR3 depletion, the chromatin, particularly H3K27me3-modified chromatin, redistributes in the cell nuclei. Topologically associating domains (TADs) that highly transcribe MATR3-associated AS L1 RNAs show decreased intra-TAD interactions in both AML12 and ES cells. MATR3 depletion increases the accessibility of H3K27me3 domains adjacent to MATR3-associated AS L1, without affecting H3K27me3 modifications. Furthermore, amyotrophic lateral sclerosis (ALS)-associated MATR3 mutants alter biophysical features of the MATR3-AS L1 RNA meshwork and cause an abnormal H3K27me3 staining. Collectively, we reveal a role of the meshwork formed by MATR3 and AS L1 RNAs in gathering chromatin in the nucleus.
摘要：
长散布的核元素（LINE）在塑造染色质状态中起着至关重要的作用，而与LINE合作的因素及其在高阶染色质组织中的作用仍然知之甚少。这里,我们发现MATR3是一种核基质蛋白，与反义LINE1（ASL1）RNA相互作用，通过相分离形成网状结构，为染色质空间组织提供动态平台。MATR3和ASL1RNAs互相影响核定位。MATR3耗尽后，染色质，特别是H3K27me3修饰的染色质，在细胞核中重新分布。高度转录MATR3相关ASL1RNA的拓扑关联域（TAD）在AML12和ES细胞中显示出降低的TAD内相互作用。MATR3耗尽增加了与MATR3相关的ASL1相邻的H3K27me3结构域的可及性，而不影响H3K27me3修饰。此外，肌萎缩侧索硬化症（ALS）相关的MATR3突变体改变了MATR3-ASL1RNA网的生物物理特征，并导致异常的H3K27me3染色。总的来说，我们揭示了MATR3和ASL1RNA在细胞核中聚集染色质中形成的网状结构的作用。
