Human Gene Set: LOPEZ_MBD_TARGETS_IMPRINTED_AND_X_LINKED
Standard name
LOPEZ_MBD_TARGETS_IMPRINTED_AND_X_LINKED
Systematic name
M4324
Brief description
X chromosome and imprinted genes up-regulated in HeLa cells (cervical cancer) after knockdown of the MBD (methyl-CpG binding domain) proteins by RNAi.
Full description or abstract
Methyl-cytosine-phosphate-guanine (CpG)-binding domain (MBD) proteins are bound to hypermethylated promoter CpG islands of tumor suppressor genes in human cancer cells, although a direct causal relationship at the genome-wide level between MBD presence and gene silencing remains to be demonstrated. To this end, we have inhibited the expression of MBD proteins in HeLa cells by short hairpin RNAs; and studied the functional consequences of MBD depletion using microarray-based expression analysis in conjunction with extensive bisulfite genomic sequencing and chromatin immunoprecipitation. The removal of MBDs results in a release of gene silencing associated with a loss of MBD occupancy in 5'-CpG islands without any change in the DNA methylation pattern. Our results unveil new targets for epigenetic inactivation mediated by MBDs in transformed cells, such as the cell adhesion protein gamma-parvin and the fibroblast growth factor 19, where we also demonstrate their bona fide tumor suppressor features. Our data support a fundamental role for MBD proteins in the direct maintenance of transcriptional repression of tumor suppressors and identify new candidate genes for epigenetic disruption in cancer cells.
Collection
C2: Curated CGP: Chemical and Genetic Perturbations
