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Learn MoreEnhancer profiling has emerged as a powerful approach for discovering the cis-regulatory elements that define transcriptional core regulatory circuits. Characteristic biochemical and biophysical attributes of chromatin mark active enhancer elements, which can be leveraged with genome-wide assay technologies for discovery. This includes chromatin immunoprecipitation followed by sequencing (ChIP-seq) for histone H3 acetylated lysine 27 (H3K27ac). Enhancers are also characterized by regions of open chromatin, hypersensitive to digestion by transposases measurable by the assay for transposase-accessible chromatin (ATAC-seq). By integrating measures of chromatin accessibility and domains of enriched H3K27 acetylation, we have generated enhancer landscapes from chronic lymphocytic leukemia (CLL) representative cell lines including MEC1, MEC2, OSU-CLL, and CII. Targeting enhancer signaling via BET bromodomain inhibition (using the inhibitor JQ1) disrupts enhancer-dependent gene expression as measured with RNA-sequencing in CLL cell lines. SOURCE: James Bradner (bradner_computation@dfci.harvard.edu) - Bradner Lab Dana-Farber Cancer Institute
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