Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers. H2A.Zac nucleosome occupancy is rapidly remodeled to flank the AR sites to initiate the formation of nucleosome-free regions and the production of AR-enhancer RNAs upon androgen treatment. Remarkably higher levels of global H2A.Zac correlate with poorer prognosis. Altogether these data demonstrate the novel contribution of H2A.Zac in activation of newly formed enhancers in prostate cancer.
Highlights d Promoter CpG islands display asymmetric border methylation encroachment in cancer d 5hmC is enriched in normal cells at CpG island shores prone to methylation spread d H3K4me1 patterns at CpG island borders are associated with the mode of encroachment d H3K4me1 disruption results in DNA methylation alterations at island borders
Highlights d scRNA-seq analysis redefines vaginal epithelial cell hierarchy d Cd271+Axin2+ cells represent ovariectomy-resistant vaginal epithelial stem cells d These cells are responsible for vaginal epithelial homeostasis and regeneration d Cd271+Axin2+ cell-derived organoids mimic vaginal epithelium in vivo
Single-cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype Graphical abstract Highlights d Drop-seq reveals a strong cancer cell heterogeneity in PyMT mammary tumors d Elf5 redefines cancer cell states toward basal-like with prometastatic features d PyMT/Elf5 tumors show cellular and molecular characteristics of involution mimicry d Involution CAFs in PyMT/Elf5 tumors interconnect the TME and cancer cells
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