An ES cell–specific NuRD complex functions through interaction with Wdr5. Mus musculus

The Nucleosome Remodeling and Deacetylase (NuRD) complex is a chromatin regulatory complex that functions as a transcriptional co-repressor in metazoans. The NuRD subunit Mbd3 is essential for targeting and assembly of a functional NuRD complex as well as embryonic stem cell (ESC) pluripotency. Three Mbd3 isoforms (Mbd3a, Mbd3b, and Mbd3c) are expressed in mouse. Here, we find that the Mbd3c isoform contains a unique 50–amino acid N-terminal region that is necessary for Mbd3c to specifically interact with the histone H3 binding protein Wdr5. Domain analyses of Wdr5 reveal that the Wdr5 H3K4/MLL binding pocket is required for interaction with Mbd3c. We find that while Mbd3c KO ESCs differentiate normally, Mbd3c is redundant with the Mbd3a and Mbd3b isoforms in regulation of gene expression and ESC pluripotency, with the unique Mbd3c N-terminus required for this redundancy. Together, our data characterize a novel NuRD complex variant that functions specifically in ESCs Overall design: Gene expression profiles generated by RNA-seq of Mbd3 isoform mutant mouse embryonic stem cells