FBXL10 and the Protection of Polycomb-bound Genes from Hypermethylation (RRBS)

ABSTRACT: Nearly all CpG-dense promoters are occupied by the multi-domain chromosomal protein FBXL10. We show here that complete inactivation of the Fbxl10 gene leads to dense de novo methylation only of the promoters that are co-occupied by both FBXL10 and by Polycomb Repressive Complexes; this results in pervasive defects in embryonic development and death of homozygous Fbxl10 mutant embryos at midgestation. Deletion of key components of Polycomb Repressive Complexes 1 and 2 did not lead to ectopic de novo methylation. These results indicate that FBXL10 defends Polycomb-occupied promoters against ectopic de novo methylation. FBXL10 is the first reported factor whose loss leads to a gain in genomic DNA methylation. DNA methylation analysis using RRBS and expression analysis using RNA-seq was performed on WT and Fbxl10T/T ES cells.

ORGANISM(S): Mus musculus

SUBMITTER: John Edwards 

PROVIDER: E-GEOD-65580 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress