CHD7 is one of the nine members of the chromodomain helicase DNA-binding family of ATP-dependent chromatin remodeling enzymes. Mutations in CHD7 give rise to CHARGE syndrome, a human condition characterized by malformation of various organs. We have now identified a novel transcript of CHD7 that is generated by alternative splicing of exon 6. The protein encoded by this variant transcript (termed CHD7 S) lacks one of the two chromodomains as well as the helicase/ATPase domain, DNA-binding domain and BRK domains of the full-length protein (CHD7 L). CHD7 S was found to localize specifically to the nucleolus in a manner dependent on a nucleolar localization signal. Over-expression of CHD7 S, as well as that of CHD7 L, resulted in an increase in 45S precursor rRNA production. Conversely, depletion of both CHD7 S and CHD7 L by RNA interference inhibited both 45S precursor rRNA production and cell proliferation to a greater extent than did depletion of CHD7 L alone. Furthermore, we found that, like CHD7 L, CHD7 S binds to Sox2 in the nucleoplasm. Unexpectedly, however, whereas over-expression of CHD7 L promoted Sox2-mediated transcriptional regulation, over-expression of CHD7 S suppressed it. These results indicate that CHD7 S functions cooperatively or antagonistically with CHD7 L in the nucleolus and nucleoplasm, respectively.
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