Identification of CHD7S as a novel splicing variant of CHD7 with functions similar and antagonistic to those of the full-length CHD7L.
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 CHD7S) lacks one of the two chromodomains as well as the helicase/ATPase domain, DNA-binding domain and BRK domains of the full-length protein (CHD7L). CHD7S was found to localize specifically to the nucleolus in a manner dependent on a nucleolar localization signal. Over-expression of CHD7S, as well as that of CHD7L, resulted in an increase in 45S precursor rRNA production. Conversely, depletion of both CHD7S and CHD7L by RNA interference inhibited both 45S precursor rRNA production and cell proliferation to a greater extent than did depletion of CHD7L alone. Furthermore, we found that, like CHD7L, CHD7S binds to Sox2 in the nucleoplasm. Unexpectedly, however, whereas over-expression of CHD7L promoted Sox2-mediated transcriptional regulation, over-expression of CHD7S suppressed it. These results indicate that CHD7S functions cooperatively or antagonistically with CHD7L in the nucleolus and nucleoplasm, respectively.
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Yasuyuki
Y
Kita
Masaaki
M
Nishiyama
Keiichi I
KI
Nakayama
D017398:Alternative Splicing; D001483:Base Sequence; D002460:Cell Line; D002466:Cell Nucleolus / Q000378:metabolism; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D023061:Gene Order; D006801:Humans; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012335:RNA, Ribosomal / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D019913:Nuclear Localization Signals; D020033:Protein Isoforms; D012335:RNA, Ribosomal; C088179:RNA, ribosomal, 45S; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D004265:DNA Helicases; C491434:CHD7 protein, human