Chromatin remodeling factor CHD5 is silenced by promoter CpG island hypermethylation in human cancer.
Changes in chromatin structure are an essential mechanism for gene regulation (transcription, replication, DNA repair and recombination). ATP-dependent chromatin-remodeling enzymes have previously been implicated in maintaining and regulating chromatin structure. These enzymes are divided into several groups including the SWI/SNF, ISWI and CHD families. Although the Chromodomain Helicase DNA-binding protein (CHD) family members are involved in key cellular processes, the disrupted regulation of their expression has not been fully assessed. An impairment of chromatin remodeling activity, mediated by promoter CpG island hypermethylation of the described candidate genes, could be key in cancer pathology. Herein, we examine the DNA methylation profiles of CHD family members (CHD1-9) in different tumor types. For all CHDs, CpG island hypermethylation was only observed at the CHD5 promoter in human cancer cell lines and primary tumors, particularly gliomas and colon and breast carcinomas. RT-qPCR analyses correlated CHD5 loss of expression with hypermethylation of the promoter, and restoration of CHD5 mRNA levels upon treatment with a DNA demethylating agent. These results underpin the epigenetic inactivation of the chromating remodeling factor CHD5 as one contributor for the aberrant structural changes of chromatin throughout the genome of the cancer cell.
Mulero-Navarro
Sonia
S
Cancer Epigenetics and Biology Program (PEBC), Catalan Institute of Oncology (ICO), Hospital Duran i Reynals, Barcelona, Catalonia, Spain.
Esteller
Manel
M
D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism*; D018899:CpG Islands / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic
D002843:Chromatin; D009419:Nerve Tissue Proteins; D004265:DNA Helicases; C471926:CHD5 protein, human