Cell differentiation is mediated by lineage-determining transcription factors. 
We show that chromodomain helicase DNA-binding domain 2 (Chd2), a SNF2 chromatin 
remodelling enzyme family member, interacts with MyoD and myogenic gene 
regulatory sequences to specifically mark these loci via deposition of the 
histone variant H3.3 prior to cell differentiation. Directed and genome-wide 
analysis of endogenous H3.3 incorporation demonstrates that knockdown of Chd2 
prevents H3.3 deposition at differentiation-dependent, but not housekeeping, 
genes and inhibits myogenic gene activation. The data indicate that MyoD 
determines cell fate and facilitates differentiation-dependent gene expression 
through Chd2-dependent deposition of H3.3 at myogenic loci prior to 
differentiation.