Exchange of associated factors directs a switch in HBO1 acetyltransferase histone tail specificity.
Exchange of associated factors directs a switch in HBO1 acetyltransferase histone tail specificity.
复制标题
DOI：
10.1101/gad.223396.113
复制
发表时间：
2013-09-15
影响因子：
10.5
通讯作者：
Côté J
中科院分区：
文献类型：
--
作者：
Lalonde ME;Avvakumov N;Glass KC;Joncas FH;Saksouk N;Holliday M;Paquet E;Yan K;Tong Q;Klein BJ;Tan S;Yang XJ;Kutateladze TG;Côté J
组蛋白乙酰转移酶（HAT）组装成多亚基复合物，靶向核小体组蛋白上的不同赖氨酸残基。在此，Lalonde等人表征了由支架蛋白的BRPF家族组装的天然HAT复合物，并显示在与JADE或BRPF 1蛋白缔合后，HBO 1 HAT的特异性从H3尾变为H4尾。还鉴定了支架蛋白内负责染色质上的组蛋白尾选择的区域。这项研究提供了关键的新的见解如何组蛋白修饰酶底物特异性的确定。组蛋白乙酰转移酶（HAT）组装成多亚基复合物，以靶向核小体组蛋白上的不同赖氨酸残基。在这里，我们表征天然HAT复合物组装的BRPF家族的支架蛋白。它们的植物同源结构域（PHD）-Zn knuckle-PHD结构域对于结合染色质是必需的，并且限于未甲基化的H3 K4，这是由相关ING亚基逆转的特异性。天然BRPF 1复合物可以含有MOZ/MORF或HBO 1作为催化乙酰转移酶亚基。有趣的是，虽然先前报道的含有JADE支架蛋白的HBO 1复合物靶向组蛋白H4，但HBO 1-BRPF 1复合物仅乙酰化染色质中的H3。我们绘制了一个小区域的N端的支架蛋白负责组蛋白尾部选择染色质。因此，与HBO 1相关的亚基的交替选择可以在H4和H3尾之间切换其特异性。这些结果揭示了HAT复合物中相关蛋白的重要新作用，以前认为这是催化亚基所固有的。
Histone acetyltransferases (HATs) assemble into multisubunit complexes that target distinct lysine residues on nucleosomal histones. Here, Lalonde et al. characterize native HAT complexes assembled by the BRPF family of scaffold proteins and show that the specificity of the HBO1 HAT changes from the H3 to the H4 tail upon association with either JADE or BRPF1 protein. A region within scaffold proteins responsible for histone tail selection on chromatin is also identified. This study provides critical new insight into how histone-modifying enzyme substrate specificity is determined. Histone acetyltransferases (HATs) assemble into multisubunit complexes in order to target distinct lysine residues on nucleosomal histones. Here, we characterize native HAT complexes assembled by the BRPF family of scaffold proteins. Their plant homeodomain (PHD)–Zn knuckle–PHD domain is essential for binding chromatin and is restricted to unmethylated H3K4, a specificity that is reversed by the associated ING subunit. Native BRPF1 complexes can contain either MOZ/MORF or HBO1 as catalytic acetyltransferase subunit. Interestingly, while the previously reported HBO1 complexes containing JADE scaffold proteins target histone H4, the HBO1–BRPF1 complex acetylates only H3 in chromatin. We mapped a small region to the N terminus of scaffold proteins responsible for histone tail selection on chromatin. Thus, alternate choice of subunits associated with HBO1 can switch its specificity between H4 and H3 tails. These results uncover a crucial new role for associated proteins within HAT complexes, previously thought to be intrinsic to the catalytic subunit.
登录
查看更多内容
影响因子：
2.9
作者：
Champagne KS;Saksouk N;Peña PV;Johnson K;Ullah M;Yang XJ;Côté J;Kutateladze TG
通讯作者：
Kutateladze TG
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
10.5
作者：
Katsumoto, Takuo;Aikawa, Yukiko;Kitabayashi, Issay
通讯作者：
Kitabayashi, Issay
影响因子：
5.3
作者：
Kueh, Andrew J.;Dixon, Mathew P.;Thomas, Tim
通讯作者：
Thomas, Tim
影响因子：
11.4
作者：
Kasten, M;Szerlong, H;Cairns, BR
通讯作者：
Cairns, BR