組蛋白有多種變異體,,在實驗胚胎學中,研究不同時期染色體上組蛋白變體如何影響發(fā)育過程是一個較大的挑戰(zhàn)。本文中,,研究者利用非洲爪蟾作為模型,研究組蛋白H3.3和它特異的分子伴侶HIRA在胚胎發(fā)育中的作用,。
研究人員發(fā)現(xiàn)組蛋白H3.3的轉(zhuǎn)錄在原腸胚形成期達到高峰,。去除H3.2和H3.3會使胚胎發(fā)育停滯在原腸胚早期,但只缺乏H3.3的胚胎會在原腸胚晚期出現(xiàn)缺陷,。此外,,下調(diào)H3.3的分子伴侶HIRA也會使胚胎發(fā)育在原腸胚晚期表現(xiàn)出缺陷。與H3.3缺乏一樣,,HIRA的下調(diào)會導致整個染色體區(qū)域H3.3富集的缺失,。研究人員據(jù)此得出,,依賴HIRA的H3.3富集在胚胎發(fā)育過程中是必需的。(生物谷 Bioon.com )
doi:10.1016/j.celrep.2012.05.006
PMC:
PMID:
A Developmental Requirement for HIRA-Dependent H3.3 Deposition Revealed at Gastrulation in Xenopus
Emmanuelle Szenker, Nicolas Lacoste, Geneviève Almouzni
Discovering how histone variants that mark distinct chromatin regions affect a developmental program is a major challenge in the epigenetics field. To assess the importance of the H3.3 histone variant and its dedicated histone chaperone HIRA, we used an established developmental model, Xenopus laevis. After the early rapid divisions exploiting a large maternal pool of both replicative H3.2 and replacement H3.3, H3.3 transcripts show a distinct peak of expression at gastrulation. Depletion of both H3.2 and H3.3 leads to an early gastrulation arrest. However, with only H3.3 depletion, defects occur at late gastrulation, impairing further development. Providing exogenous H3.3 mRNAs, but not replicative H3.2 mRNAs, rescues these defects. Notably, downregulation of the H3.3 histone chaperone HIRA similarly impairs late gastrulation, and we find a global defect in H3.3 incorporation into chromatin comparable to H3.3 depletion. We discuss how specific HIRA-dependent H3.3 deposition is required for chromatin dynamics during gastrulation.