Endogenous mammalian histone H3.3 exhibits chromatin-related functions during development.
Endogenous mammalian histone H3.3 exhibits chromatin-related functions during development.
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DOI：
10.1186/1756-8935-6-7
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发表时间：
2013-04-09
影响因子：
3.9
通讯作者：
Knoepfler PS
中科院分区：
文献类型：
--
作者：
Bush KM;Yuen BT;Barrilleaux BL;Riggs JW;O'Geen H;Cotterman RF;Knoepfler PS
组蛋白变体H3.3在调节染色质状态和转录中起关键作用。然而，内源性H3.3在哺乳动物细胞和发育过程中的作用还没有得到彻底的研究。为了解决这一差距，我们报告了H3.3编码基因H3 f3 b的靶向破坏的小鼠和细胞的生产和表型分析。H3 f3 b敲除（KO）小鼠表现出半致死表型，其至少部分可追溯至缺陷性细胞分裂和染色体分离。H3 f3 b KO细胞具有广泛的异位CENP-A蛋白定位，这提示了缺陷性染色体分离的一种可能机制。KO细胞具有异常的核型和细胞周期谱。转录组和常染色质相关的表观基因组受到小鼠胚胎成纤维细胞（MEFs）中H3 f3 b丢失的中度影响，其中本体论最显著地指向染色质调控和组蛋白编码基因的变化。H3 f3 b KO小鼠存活至成熟的数量减少，几乎所有来自两种性别的存活小鼠都是不育的。总之，我们的研究表明，内源性哺乳动物组蛋白H3.3在调节染色质和染色体功能方面具有重要作用，而这些功能又对细胞分裂、基因组完整性和发育至关重要。
The histone variant H3.3 plays key roles in regulating chromatin states and transcription. However, the role of endogenous H3.3 in mammalian cells and during development has been less thoroughly investigated. To address this gap, we report the production and phenotypic analysis of mice and cells with targeted disruption of the H3.3-encoding gene, H3f3b. H3f3b knockout (KO) mice exhibit a semilethal phenotype traceable at least in part to defective cell division and chromosome segregation. H3f3b KO cells have widespread ectopic CENP-A protein localization suggesting one possible mechanism for defective chromosome segregation. KO cells have abnormal karyotypes and cell cycle profiles as well. The transcriptome and euchromatin-related epigenome were moderately affected by loss of H3f3b in mouse embryonic fibroblasts (MEFs) with ontology most notably pointing to changes in chromatin regulatory and histone coding genes. Reduced numbers of H3f3b KO mice survive to maturity and almost all survivors from both sexes are infertile. Taken together, our studies suggest that endogenous mammalian histone H3.3 has important roles in regulating chromatin and chromosome functions that in turn are important for cell division, genome integrity, and development.
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影响因子：
10.5
作者：
Drane, Pascal;Ouararhni, Khalid;Hamiche, Ali
通讯作者：
Hamiche, Ali
影响因子：
64.5
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
通讯作者：
Allis CD
变体组蛋白 H3.3 对颅神经嵴外间质潜能的重要作用。
影响因子：
4.5
作者：
Cox SG;Kim H;Garnett AT;Medeiros DM;An W;Crump JG
通讯作者：
Crump JG
影响因子：
7
作者：
Delbarre E;Ivanauskiene K;Küntziger T;Collas P
通讯作者：
Collas P
影响因子：
11.4
作者：
Braunschweig, Ulrich;Hogan, Greg J.;van Steensel, Bas
通讯作者：
van Steensel, Bas