CHD1 was also recently implicated in pluripotency, through its ability to maintain the open chromatin configuration that is characteristic of mouse ESCs67. Mouse ESCs in which Chd1 has been knocked down using RNAi maintain many of the characteristics of self-renewing ESCs, but they are defective in multilineage differentiation. CHD1 associates with the promoters of active genes and prevents the accumulation of heterochromatin through an unknown mechanism. The conversion of euchromatin to heterochromatin is presumably the cause of the impaired lineage commitment of CHD1-deficient ESCs, because the induction of differentiation transcription programs potentially requires all genes to be generally accessible, including transcriptionally silent developmental genes in ESCs. Although it is not known how CHD1 maintains open chromatin structure, one intriguing possibility is that it is involved in incorporating H3.3 into the chromatin. Because the phenotypes observed in RNAi studies are sometimes unreliable, the implication that CHD1 is involved in pluripotency will need to be confirmed by analysing embryos with null mutations of Chd1.
