title: A requirement for DICER to maintain full promoter CpG island hypermethylation in human cancer cells.
abstract: Promoter hypermethylation is a prevalent phenomenon, found in virtually all cancer types studied thus far, and accounts for tumor suppressor gene silencing in the absence of genetic mutations. The mechanism behind the establishment and maintenance of such aberrant hypermethylation has been under intense study. Here, we have uncovered a link between aberrant gene silencing associated with promoter CpG island DNA methylation and the siRNA/miRNA processing enzyme, DICER, in human cancer cells. By comparing demethylated HCT116 colon cancer cells with HCT116 cells genetically rendered hypomorphic for DICER, we identified a group of epigenetically silenced genes that became reactivated in the absence of functional DICER. This reactivation is associated with a dramatic loss of localized promoter DNA hypermethylation. Thus, intact DICER is required to maintain full promoter DNA hypermethylation of select epigenetically silenced loci in human cancer cells.
authors.affiliation: Genomic Medicine Institute, Lerner Research Institute, Cleveland, Ohio, USA. tinga@ccf.org
authors.forename: Angela H
authors.initials: AH
authors.lastname: Ting
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Leslie
authors.initials: L
authors.lastname: Cope
authors.forename: Kornel E
authors.initials: KE
authors.lastname: Schuebel
authors.forename: Byron H
authors.initials: BH
authors.lastname: Lee
authors.forename: Minoru
authors.initials: M
authors.lastname: Toyota
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
authors.forename: Takashi
authors.initials: T
authors.lastname: Tokino
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Baylin
mesh_terms: D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D043244:Ribonuclease III