Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome, 00185 Rome, Italy.
Institute of Molecular Biology and Pathology (IBPM), Consiglio Nazionale delle Ricerche (CNR), Sapienza University of Rome, 00185 Rome, Italy.
Cells. 2023 May 9;12(10):1348. doi: 10.3390/cells12101348.
ATP-dependent chromatin remodeling complexes are involved in nucleosome sliding and eviction and/or the incorporation of histone variants into chromatin to facilitate several cellular and biological processes, including DNA transcription, replication and repair. The DOM/TIP60 chromatin remodeling complex of contains 18 subunits, including the DOMINO (DOM), an ATPase that catalyzes the exchange of the canonical H2A with its variant (H2A.V), and TIP60, a lysine-acetyltransferase that acetylates H4, H2A and H2A.V histones. In recent decades, experimental evidence has shown that ATP-dependent chromatin remodeling factors, in addition to their role in chromatin organization, have a functional relevance in cell division. In particular, emerging studies suggested the direct roles of ATP-dependent chromatin remodeling complex subunits in controlling mitosis and cytokinesis in both humans and However, little is known about their possible involvement during meiosis. The results of this work show that the knockdown of 12 of DOM/TIP60 complex subunits generates cell division defects that, in turn, cause total/partial sterility in males, providing new insights into the functions of chromatin remodelers in cell division control during gametogenesis.
ATP 依赖的染色质重塑复合物参与核小体滑动和逐出，以及/或者将组蛋白变体掺入染色质中，以促进包括 DNA 转录、复制和修复在内的多种细胞和生物学过程。包含 18 个亚基的 DOM/TIP60 染色质重塑复合物，其中包括 DOMINO（DOM），一种 ATP 酶，可催化将典型的 H2A 与其变体（H2A.V）进行交换，以及 TIP60，一种赖氨酸乙酰转移酶，可乙酰化 H4、H2A 和 H2A.V 组蛋白。近几十年来，实验证据表明，除了在染色质组织中的作用外，ATP 依赖的染色质重塑因子在细胞分裂中具有功能相关性。特别是，新兴的研究表明，ATP 依赖的染色质重塑复合物亚基在控制人类和 中的有丝分裂和胞质分裂中具有直接作用。然而，对于它们在减数分裂过程中的可能参与，知之甚少。这项工作的结果表明，敲低 12 个 DOM/TIP60 复合物亚基会导致细胞分裂缺陷，进而导致 雄性的完全/部分不育，这为染色质重塑因子在配子发生过程中的细胞分裂控制中的功能提供了新的见解。
