The histone variant macroH2A suppresses @entity320 progression through regulation of XXXX .

@entity1 @entity5 @entity41183 @entity3 @entity14 @entity320
@entity5 is a disease consisting of both genetic and epigenetic changes. Although increasing evidence demonstrates that @entity5 progression entails chromatin-mediated changes such as DNA methylation, the role of histone variants in @entity5 initiation and progression currently remains unclear. Histone variants replace conventional histones within the nucleosome and confer unique biological functions to chromatin. Here we report that the histone variant macroH2A (mH2A) suppresses @entity5 progression of @entity320 . Loss of mH2A isoforms, histone variants generally associated with condensed chromatin and fine-tuning of developmental gene expression programs, is positively correlated with increasing malignant phenotype of @entity320 cells in culture and @entity1 tissue samples. Knockdown of mH2A isoforms in @entity320 cells of low malignancy results in significantly increased proliferation and migration in vitro and growth and @entity3 in vivo. Restored expression of mH2A isoforms rescues these malignant phenotypes in vitro and in vivo. We demonstrate that the @entity5 -promoting function of mH2A loss is mediated, at least in part, through direct transcriptional upregulation of @entity41183 . Suppression of @entity41183 , a @entity14 oncogene, inhibits proliferation of @entity320 cells, and knockdown of @entity41183 in cells depleted of mH2A suppresses the proliferative advantage induced by mH2A loss. Moreover, a significant inverse correlation between mH2A and @entity41183 expression levels exists in @entity320 @entity1 samples. Taken together, our results demonstrate that mH2A is a critical component of chromatin that suppresses the development of @entity320 , a highly intractable cutaneous @entity5 .
