Project description:We performed Hi-C, Micro-C, and capture Micro-C in human prostate cancer cells and compared chromatin interactions called using different methods. By integrating Micro-C with NOMe-seq, ChIP-seq, and RNA-seq, we investigated the relationships among nucleosome positioning of regulatory elements, chromatin interactions, and transcription. This work provides a framework for understanding the chromatin interactions among regulatory elements, nucleosome-depleted regions, and transcription.
Project description:Cis-regulatory elements coordinate the regulation of their targeted genes’ expression. However, the joint measurement of cis-regulatory elements’ activities and their interactions in spatial proximity is limited by the current sequencing approaches. We describe a method, NOMe-HiC, which simultaneously captures single nucleotide polymorphisms, DNA methylation, chromatin accessibility (GpC methyltransferase footprints), and chromosome conformation changes from the same DNA molecule, together with the transcriptome, in a single assay. NOMe-HiC shows high concordance with state-of-the-art mono-omic assays across different molecular measurements and reveals coordinated chromatin accessibility at distal genomic segments in spatial proximity and novel types of long-range allele-specific chromatin accessibility.
Project description:Chromatin accessibility plays a key role in epigenetic regulation of gene activation and silencing. Open chromatin regions allow regulatory elements such as transcription factors and polymerases to bind for gene expression while closed chromatin regions prevent the activity of transcriptional machinery. Nucleosome occupancy and methylome sequencing (NOMe-seq) has been developed for simultaneously profiling of chromatin accessibility and DNA methylation on single molecules. In this study, we combined the principle of NOMe-seq with targeted bisulfite sequencing method to analyze the genome-wide nucleosome occupancy and chromatin accessibility in the promoter and enhancer regions of over 20,000 genes. In addition, we developed CAME, a seed-extension based approach that identifies chromatin accessibility from NOMe-seq. Our results show that our method not only can precisely identify chromatin accessibility but also outperforms other methods.
