title: Promoter histone H3K27 methylation in the control of IGF2 imprinting in human tumor cell lines.
abstract: Aberrant imprinting of the insulin-like growth factor II (IGF2) gene is a molecular hallmark of many tumors. Reactivation of the normally suppressed maternal allele leads to upregulation of the growth factor that promotes tumor growth. However, the mechanisms underlying the loss of imprinting (LOI) remain poorly defined. We examined the epigenotypes at the gene promoters that control IGF2 allelic expression. Using chromatin immunoprecipitation, we found that in cells characterized by maintenance of IGF2 imprinting, three IGF2 promoters were differentially modified, with the suppressed allele heavily methylated at histone H3K27 while the active allele was unmethylated. In the LOI tumors, however, both alleles were unmethylated, and correspondingly there was no binding of SUZ12, the docking factor of the polycomb repressive complex 2 (PRC2), and of the zinc finger-containing transcription factor (CTCF) that recruits the PRC2. Using chromatin conformation capture, we found that the CTCF-orchestrated intrachromosomal loop between the IGF2 promoters and the imprinting control region was abrogated in cells with LOI. SUZ12, which docks the PRC2 to IGF2 promoters for H3K27 methylation, was downregulated in LOI cells. These data reveal a new epigenetic control pathway related to the loss of IGF2 imprinting in tumors.
authors: Shenzhen Beike Cell Engineering Research Institute, Shenzhen, China.
authors: Tao
authors: T
authors: Li
authors: Huiling
authors: H
authors: Chen
authors: Wei
authors: W
authors: Li
authors: Jiuwei
authors: J
authors: Cui
authors: Guanjun
authors: G
authors: Wang
authors: Xiang
authors: X
authors: Hu
authors: Andrew R
authors: AR
authors: Hoffman
authors: Jifan
authors: J
authors: Hu
mesh_terms: D000483:Alleles; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D019073:HT29 Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism*; D008745:Methylation; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; D006657:Histones; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C430461:SUZ12 protein, human; D014157:Transcription Factors; D007335:Insulin-Like Growth Factor II; D063151:Polycomb Repressive Complex 2
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