Department of Genome Sciences, University of Washington, Foege S310A, 1705 NE Pacific Street, Box 355065, Seattle, WA 98195, USA.
Genome Biol. 2011;12(5):R43. doi: 10.1186/gb-2011-12-5-r43. Epub 2011 May 11.
The development of complex organisms is believed to involve progressive restrictions in cellular fate. Understanding the scope and features of chromatin dynamics during embryogenesis, and identifying regulatory elements important for directing developmental processes remain key goals of developmental biology.
We used in vivo DNaseI sensitivity to map the locations of regulatory elements, and explore the changing chromatin landscape during the first 11 hours of Drosophila embryonic development. We identified thousands of conserved, developmentally dynamic, distal DNaseI hypersensitive sites associated with spatial and temporal expression patterning of linked genes and with large regions of chromatin plasticity. We observed a nearly uniform balance between developmentally up- and down-regulated DNaseI hypersensitive sites. Analysis of promoter chromatin architecture revealed a novel role for classical core promoter sequence elements in directing temporally regulated chromatin remodeling. Another unexpected feature of the chromatin landscape was the presence of localized accessibility over many protein-coding regions, subsets of which were developmentally regulated or associated with the transcription of genes with prominent maternal RNA contributions in the blastoderm.
Our results provide a global view of the rich and dynamic chromatin landscape of early animal development, as well as novel insights into the organization of developmentally regulated chromatin features.
人们认为复杂生物的发育涉及细胞命运的逐渐限制。了解胚胎发生过程中染色质动态的范围和特征,并确定指导发育过程的重要调控元件,仍然是发育生物学的主要目标。
我们使用体内 DNaseI 敏感性来绘制调控元件的位置,并探索果蝇胚胎发育的前 11 小时内不断变化的染色质景观。我们鉴定了数千个保守的、发育动态的、远端的 DNaseI 超敏位点,这些位点与相关基因的空间和时间表达模式以及染色质可塑性的大片段有关。我们观察到发育上调和下调的 DNaseI 超敏位点之间几乎均匀的平衡。启动子染色质结构的分析揭示了经典核心启动子序列元件在指导时间调节染色质重塑中的新作用。染色质景观的另一个意外特征是许多蛋白编码区存在局部可及性,其中一些受发育调控或与母源 RNA 大量贡献的胚盘中基因的转录有关。
我们的研究结果提供了早期动物发育丰富而动态的染色质景观的整体视图,并为发育调控染色质特征的组织提供了新的见解。