Project description:Current genome-wide detection of chromatin accessibility uses the assay for transposase-accessible chromatin (ATAC-seq). To a provide panoramic view of the chromatin accessibility landscape in prostate cancer and normal prostate, we performed ATAC-seq in 20 pairs of prostate cancer tissues and matched adjacent tissues. Assay of transposase accessible chromatin with high-throughput sequencing (ATAC-seq) for 20 pairs of prostate cancer tissues and matched adjacent tissues.
Project description:To construct the enhancer transcription expression profile, we performed RNA-seq in 20 pairs of prostate cancer tissues and matched adjacent tissues. We then performed enhancer transcription expression profiling analysis using data obtained from RNA-seq of 20 pairs of samples.
Project description:<p>In this study we profile the epigenomic enhancer landscapes of CLL B cells (CD19+/CD5+) harvested from peripheral blood of patients from our Center. Included are results of ChIPseq profiling using chromatin immunoprecipitation of the enhancer histone mark H3K27ac (acetylated lysine 27 on histone H3), and open chromatin profiles using ATAC-seq (assay for transposase accessible chromatin). These profiles are used to define the global enhancer and super enhancer landscape of CLL B cells, and to derive active transcription factor networks associated with this disease. Also included are H3K27ac ChIP-seq and ATAC-seq datasets for non-CLL B cells obtained from the peripheral blood of normal adult donors.</p>
Project description:Recent studies suggest a hierarchical model in which lineage-determining factors act in a collaborative manner to select and prime cell-specific enhancers, thereby enabling signal-dependent transcription factors to bind and function in a cell type-specific manner. Consistent with this model, TLR4 signaling primarily regulates macrophage gene expression through a pre-existing enhancer landscape. However, TLR4 signaling also induces priming of ~3000 enhancer-like regions de novo, enabling visualization of intermediates in enhancer selection and activation. Unexpectedly, we find that enhancer transcription precedes local mono- and di-methylation of histone H3 lysine 4 (H3K4me1/2). H3K4 methylation at de novo enhancers is primarily dependent on the histone methyltransferases Mll1, Mll2/4 and Mll3, and is significantly reduced by inhibition of RNA polymerase II elongation. Collectively, these findings suggest an essential role of enhancer transcription in H3K4me1/2 deposition at de novo enhancers that is independent of potential functions of the resulting eRNA transcripts. ChIP-Seq and Gro-Seq profiling was performed in thioglycollate-elicited peritoneal macrophages, PU.1-/- and PUER cells treated as indicated.
Project description:Amplification of the androgen receptor (AR) locus is the most frequent alteration in metastatic treatment resistant prostate cancer. Recently it was discovered that an enhancer of the AR is co-amplified with the AR gene body and contributes to increased AR transcription and resistance to androgen deprivation therapy. However, the mechanism of enhancer activation in advanced disease is unknown. Here, we used functional genetic screening to identify transcription factors that bind to the AR enhancer and are required for enhancer mediated AR transcription. We validated binding of the transcription factors, HOXB13, GATA2, and TFAP2C in patient derived xenografts and demonstrated differential effects on features associated with active chromatin state including H3K27ac, DNA accessibility, and enhancer-promoter interaction frequency. Interestingly, the AR enhancer belongs to a set of regulatory elements that requires HOXB13 to maintain FOXA1 binding, uncovering a novel role for HOXB13 in castration-resistant prostate cancer. This work provides a framework to functionally identify trans-acting factors required for activation of disease related noncoding regulatory elements.