ESCO1/2's roles in chromosome structure and interphase chromatin organization.
ESCO1/2's roles in chromosome structure and interphase chromatin organization.
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DOI：
10.1101/gad.306084.117
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发表时间：
2017-11-01
影响因子：
10.5
通讯作者：
Branzei D
中科院分区：
文献类型：
--
作者：
Kawasumi R;Abe T;Arakawa H;Garre M;Hirota K;Branzei D
在这项研究中，Kawasumi等人研究了介导SMC 3乙酰化和姐妹染色单体凝聚（SCC）的ESCO 1/2乙酰转移酶如何相互作用并促进染色体结构和增殖。他们使用ESCO 1/2、SMC 3乙酰化和粘着蛋白去除剂WAPL突变的鸡DT 40细胞系，表明脊椎动物ESCO 1/2的凝聚力建立与间期染色质结构形成有关。ESCO 1/2乙酰转移酶介导SMC 3乙酰化和姐妹染色单体凝聚力（SCC）是基因组完整性和发育所需的差异。在这里，我们建立了鸡DT 40细胞系与突变的ESCO 1/2，SMC 3乙酰化，和cohesin去除WAPL。ESCO 1和ESCO 2都促进SCC，而ESCO 2是增殖和着丝粒完整性所必需的。ESCO 1过表达完全抑制了ESCO 2细胞的缓慢增殖和着丝粒分离表型，但仅部分抑制了其染色体臂SCC缺陷。由于有丝分裂染色体分离受损，ESCO 1和ESCO 2的同时失活导致死亡。wapl和乙酰基模拟smc 3-QQ突变都不能挽救esco 1和esco 2的致死性。值得注意的是，esco 1，esco 2，wapl条件突变体表现出非常严重的增殖缺陷与灾难性的有丝分裂和异常的间期染色质组织模式。结果表明，脊椎动物ESCO 1/2的凝聚力的建立与间期染色质结构的形成有关，这是一种新发现的粘着蛋白乙酰转移酶的功能，既具有根本性又具有医学相关性。
In this study, Kawasumi et al. researched how ESCO1/2 acetyltransferases mediating SMC3 acetylation and sister chromatid cohesion (SCC) interact and contribute to chromosome structure and proliferation. Using chicken DT40 cell lines with mutations in ESCO1/2, SMC3 acetylation, and the cohesin remover WAPL, they show that cohesion establishment by vertebrate ESCO1/2 is linked to interphase chromatin architecture formation. ESCO1/2 acetyltransferases mediating SMC3 acetylation and sister chromatid cohesion (SCC) are differentially required for genome integrity and development. Here we established chicken DT40 cell lines with mutations in ESCO1/2, SMC3 acetylation, and the cohesin remover WAPL. Both ESCO1 and ESCO2 promoted SCC, while ESCO2 was additionally and specifically required for proliferation and centromere integrity. ESCO1 overexpression fully suppressed the slow proliferation and centromeric separation phenotypes of esco2 cells but only partly suppressed its chromosome arm SCC defects. Concomitant inactivation of ESCO1 and ESCO2 caused lethality owing to compromised mitotic chromosome segregation. Neither wapl nor acetyl-mimicking smc3-QQ mutations rescued esco1 esco2 lethality. Notably, esco1 esco2 wapl conditional mutants showed very severe proliferation defects associated with catastrophic mitoses and also abnormal interphase chromatin organization patterns. The results indicate that cohesion establishment by vertebrate ESCO1/2 is linked to interphase chromatin architecture formation, a newly identified function of cohesin acetyltransferases that is both fundamentally and medically relevant.
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ECO1的锌指在姐妹染色单体内聚会期间增强其乙酰转移酶活性。
影响因子：
14.9
作者：
Onn I;Guacci V;Koshland DE
通讯作者：
Koshland DE
影响因子：
64.5
作者：
Haarhuis JHI;van der Weide RH;Blomen VA;Yáñez-Cuna JO;Amendola M;van Ruiten MS;Krijger PHL;Teunissen H;Medema RH;van Steensel B;Brummelkamp TR;de Wit E;Rowland BD
通讯作者：
Rowland BD
影响因子：
--
作者：
Abe T;Kawasumi R;Arakawa H;Hori T;Shirahige K;Losada A;Fukagawa T;Branzei D
通讯作者：
Branzei D
影响因子：
10.5
作者：
Neelsen, Kai J.;Zanini, Isabella M. Y.;Lopes, Massimo
通讯作者：
Lopes, Massimo
影响因子：
3.3
作者：
Guacci V;Koshland D
通讯作者：
Koshland D