A high-resolution 3D epigenomic map reveals insights into the creation of the prostate cancer transcriptome

高分辨率 3D 表观基因组图谱揭示前列腺癌转录组的形成

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作者:Suhn Kyong Rhie, Andrew A Perez, Fides D Lay, Shannon Schreiner, Jiani Shi, Jenevieve Polin, Peggy J Farnham

Abstract

To better understand the impact of chromatin structure on regulation of the prostate cancer transcriptome, we develop high-resolution chromatin interaction maps in normal and prostate cancer cells using in situ Hi-C. By combining the in situ Hi-C data with active and repressive histone marks, CTCF binding sites, nucleosome-depleted regions, and transcriptome profiling, we identify topologically associating domains (TADs) that change in size and epigenetic states between normal and prostate cancer cells. Moreover, we identify normal and prostate cancer-specific enhancer-promoter loops and involved transcription factors. For example, we show that FOXA1 is enriched in prostate cancer-specific enhancer-promoter loop anchors. We also find that the chromatin structure surrounding the androgen receptor (AR) locus is altered in the prostate cancer cells with many cancer-specific enhancer-promoter loops. This creation of 3D epigenomic maps enables a better understanding of prostate cancer biology and mechanisms of gene regulation.

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