An open chromatin largely devoid of heterochromatin is a hallmark of stem cells. It remains unknown whether an open chromatin is necessary for the differentiation potential of stem cells, and which molecules are needed to maintain open chromatin. Here we show that the chromatin remodelling factor Chd1 is required to maintain the open chromatin of pluripotent mouse embryonic stem cells. Chd1 is a euchromatin protein that associates with the promoters of active genes, and downregulation of Chd1 leads to accumulation of heterochromatin. Chd1-deficient embryonic stem cells are no longer pluripotent, because they are incapable of giving rise to primitive endoderm and have a high propensity for neural differentiation. Furthermore, Chd1 is required for efficient reprogramming of fibroblasts to the pluripotent stem cell state. Our results indicate that Chd1 is essential for open chromatin and pluripotency of embryonic stem cells, and for somatic cell reprogramming to the pluripotent state. In many stem cells, from flatworms to mammals, the chromatin is largely devoid of the condensed from, heterochromatin, so is openly accessible to transcriptional regulators. An RNA interference screen for novel regulators in mouse embryo cells now shows that the chromatin remodelling factor Chd1 is essential for the maintenance of open chromatin and pluripotency of embryonic cells, and for somatic cell reprogramming to pluripotency. This is direct evidence of a causal relationship between open chromatin and pluripotency. Chd1 is highly expressed in both germline and adult stem cells, raising the possibility that the relationship between open chromatin and differentiation potential of stem cells is a general phenomenon. A hallmark of stem cells is an open chromatin largely devoid of heterochromatin, but which molecules are required to maintain it is unknown, as well as whether an open chromatin is necessary for the differentiation potential of stem cells. Here, the chromatin remodelling factor Chd1 is shown to be required to maintain the open chromatin state of pluripotent mouse embryonic stem cells and to be essential for the pluripotency of these cells.

Chd1 regulates open chromatin and pluripotency of embryonic stem cells