Lu Falong, Liu Yuting, Inoue Azusa, Suzuki Tsukasa, Zhao Keji, Zhang Yi
Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
Systems Biology Center, Division of Intramural Research, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
Cell. 2016 Jun 2;165(6):1375-1388. doi: 10.1016/j.cell.2016.05.050.
How the chromatin regulatory landscape in the inner cell mass cells is established from differentially packaged sperm and egg genomes during preimplantation development is unknown. Here, we develop a low-input DNase I sequencing (liDNase-seq) method that allows us to generate maps of DNase I-hypersensitive site (DHS) of mouse preimplantation embryos from 1-cell to morula stage. The DHS landscape is progressively established with a drastic increase at the 8-cell stage. Paternal chromatin accessibility is quickly reprogrammed after fertilization to the level similar to maternal chromatin, while imprinted genes exhibit allelic accessibility bias. We demonstrate that transcription factor Nfya contributes to zygotic genome activation and DHS formation at the 2-cell stage and that Oct4 contributes to the DHSs gained at the 8-cell stage. Our study reveals the dynamic chromatin regulatory landscape during early development and identifies key transcription factors important for DHS establishment in mammalian embryos.
在植入前发育过程中，内细胞团细胞中的染色质调控格局是如何从包装方式不同的精子和卵子基因组建立起来的，目前尚不清楚。在这里，我们开发了一种低输入量的DNase I测序（liDNase-seq）方法，该方法使我们能够生成从1细胞期到桑葚胚期的小鼠植入前胚胎的DNase I超敏位点（DHS）图谱。DHS格局是逐步建立的，在8细胞期有急剧增加。父本染色质的可及性在受精后迅速重编程至与母本染色质相似的水平，而印记基因表现出等位基因可及性偏差。我们证明转录因子Nfya在2细胞期有助于合子基因组激活和DHS形成，而Oct4有助于在8细胞期获得DHS。我们的研究揭示了早期发育过程中动态的染色质调控格局，并确定了对哺乳动物胚胎中DHS建立至关重要的关键转录因子。
