ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain.
ICBP90, inverted CCAAT box-binding protein of 90 kDa, has been reported as a regulator of topoisomerase IIalpha expression. We present evidence here that ICBP90 binds to methyl-CpG when at least one symmetrically methylated-CpG dinucleotides is presented as its recognition sequence. A SET and RING finger-associated (SRA) domain accounts for the high binding affinity of ICBP90 for methyl-CpG dinucleotides. This protein constitutes a complex with HDAC1 also via its SRA domain, and bound to methylated promoter regions of various tumor suppressor genes, including p16INK4Aand p14ARF, in cancer cells. It has been reported that expression of ICBP90 was upregulated by E2F-1, and we confirmed that the upregulation was caused by binding of E2F-1 to the intron1 of ICBP90, which contains two E2F-1-binding motifs. Our data also revealed accumulation of ICBP90 in breast-cancer cells, where it might suppress expression of tumor suppressor genes through deacetylation of histones after recruitment of HDAC1. The data reported here suggest that ICBP90 is involved in cell proliferation by way of methylation-mediated regulation of certain genes.
Unoki
Motoko
M
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shiorokanedai, Minato-ku, Tokyo 108-8639, Japan.
Nishidate
Toshihiko
T
Nakamura
Yusuke
Y
D001943:Breast Neoplasms; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005260:Female; D016147:Genes, Tumor Suppressor; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007668:Kidney; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D044767:Ubiquitin-Protein Ligases
D022762:CCAAT-Enhancer-Binding Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D015226:Dinucleoside Phosphates; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D011994:Recombinant Proteins; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; C493753:E2F1 protein, human; C015772:CpG dinucleotide; C406364:UHRF1 protein, human; C110550:HDAC1 protein, human