This mechanism involves the binding of BRCA1 gene products to the promoter region of miRNA-155 (a known oncomiR), where they mediate epigenetic repression through protein-protein interactions with histone deacetylase 2. Interestingly, what emerges from this study is that R1699Q products retain DNA repair activities.
Further investigation of these clusters revealed that estrogen mediates epigenetic repression of MT1 cluster in ERα + breast cancer cell lines.
Despite our data supporting a notion that estrogen mediates epigenetic repression of the MT1 gene cluster in MCF7 cells, the underlying mechanism of what triggers this long-range coordinated repression process remains obscured.
To further investigate whether estrogen mediates epigenetic repression of the cluster in ERα + breast cancer cell lines, we conducted E2 and DAC treatment in various breast cancer cell types.
Our results showed that DZNep induced a re-expression of RAR beta 2 suggesting that DNA hypermethylation is not a predominant mechanism of silencing of RAR beta 2. It is also well known that the polycomb complex PRC2 recruits histone deacetylase proteins at the promoter region of target genes and subsequently mediates epigenetic transcriptional repression.
Its epigenetic repression, mediated by morphogens such as Wnt, Shh, Necdin, and Dlk1, induces a myofibroblastic cell fate.
Vernalization is the acceleration of flowering following prolonged cold exposure and is mediated by cold-induced epigenetic repression of the Polycomb target gene and floral repressor FLC.
For example, the Xist noncoding RNA, mediates dosage compensation and epigenetic repression by coating the inactive X chromosome in mammals.
Importantly, this aberrant epigenetic repression can be redressed clinically by depleting DNA methyltransferase 1 (DNMT1, a central component of the epigenetic network that mediates transcription repression) using the deoxycytidine analogue decitabine at non-cytotoxic concentrations.
Fig. 2 A model of epigenetic repression of transposable elements (TE) in rice.
