Distinct factors control histone variant H3.3 localization at specific genomic regions.
Distinct factors control histone variant H3.3 localization at specific genomic regions.
复制标题
DOI：
10.1016/j.cell.2010.01.003
复制
发表时间：
2010-03-05
期刊：
影响因子：
64.5
通讯作者：
Allis CD
中科院分区：
文献类型：
--
作者：
Goldberg AD;Banaszynski LA;Noh KM;Lewis PW;Elsaesser SJ;Stadler S;Dewell S;Law M;Guo X;Li X;Wen D;Chapgier A;DeKelver RC;Miller JC;Lee YL;Boydston EA;Holmes MC;Gregory PD;Greally JM;Rafii S;Yang C;Scambler PJ;Garrick D;Gibbons RJ;Higgs DR;Cristea IM;Urnov FD;Zheng D;Allis CD
组蛋白H3变体的整合与细胞状态的表观遗传记忆有关。我们利用锌指核酸酶进行基因组编辑来标记内源性H3.3，报道了哺乳动物胚胎干细胞（ES细胞）和神经前体细胞中H3变体的全基因组图谱。H3.3的全基因组模式取决于氨基酸序列，并随着细胞在发育调控位点的分化而改变。H3.3的分子伴侣Hira是H3.3在活跃和受抑制基因处富集所必需的。令人惊讶的是，Hira对于H3.3在端粒和许多转录因子结合位点的定位不是必需的。免疫亲和纯化和质谱分析表明，Atrx和Daxx蛋白以不依赖Hira的方式与H3.3结合。Atrx对于H3.3在端粒处不依赖Hira的定位以及端粒RNA的抑制是必需的。我们的数据表明，多种不同的因子负责H3.3在哺乳动物细胞特定基因组位置的定位。
The incorporation of histone H3 variants has been implicated in the epigenetic memory of cellular state. Using genome editing with zinc finger nucleases to tag endogenous H3.3, we report genome-wide profiles of H3 variants in mammalian embryonic stem (ES) cells and neuronal precursor cells. Genome-wide patterns of H3.3 are dependent on amino acid sequence, and change with cellular differentiation at developmentally regulated loci. The H3.3 chaperone Hira is required for H3.3 enrichment at active and repressed genes. Strikingly, Hira is not essential for localization of H3.3 at telomeres and many transcription factor binding sites. Immunoaffinity purification and mass spectrometry reveal that the proteins Atrx and Daxx associate with H3.3 in a Hira-independent manner. Atrx is required for Hira-independent localization of H3.3 at telomeres, and for the repression of telomeric RNA. Our data demonstrate that multiple and distinct factors are responsible for H3.3 localization at specific genomic locations in mammalian cells.
登录
查看更多内容
影响因子：
64.8
作者：
Gaspar-Maia A;Alajem A;Polesso F;Sridharan R;Mason MJ;Heidersbach A;Ramalho-Santos J;McManus MT;Plath K;Meshorer E;Ramalho-Santos M
通讯作者：
Ramalho-Santos M
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
48
作者：
Cloonan, Nicole;Forrest, Alistair R. R.;Grimmond, Sean M.
通讯作者：
Grimmond, Sean M.
影响因子：
64.5
作者：
Goldberg, Aaron D.;Allis, C. David;Bernstein, Emily
通讯作者：
Bernstein, Emily
影响因子：
56.9
作者：
Azzalin, Claus M.;Reichenbach, Patrick;Lingner, Joachim
通讯作者：
Lingner, Joachim