Inhibition of the histone methyltrasferares DOT1L deregulates hormone responsive breast cancer cells methylome
Estrogen Receptor alpha (ERa) is the master regulator of estrogen signaling in hormone-responsive breast cancer (BC), however epigenetic mechanisms, including DNA methylation, are emerging as key processes for regulation of critical cell functions including tumorigenesis. We have recently reported the epigenetic writer DOT1L (DOT1 Like Histone Lysine Methyltransferase) to associated to ERa, part of chromatin bound multiprotein complex and that the pharmacological inhibition of this enzyme reduces the transcription rate of several genes involved in ERa-mediated signaling leading to inhibition of BC cell proliferation. Here, we investigated the functional impact of DOT1L inhibition on methylome changes in BC and its possible contribution to deregulation of transcriptional pathways associated to the progression of this disease.