A cis-regulatory lexicon of DNA motif combinations mediating cell type-specific gene regulation [MPRA]

ABSTRACT: Abstract: Gene expression is controlled by transcription factors (TFs) that bind cognate DNA motifs in cis-regulatory elements (CREs), however, the combinations of motifs that mediate cell type-specific gene regulation are undefined. Chromatin accessibility, TF footprinting, and H3K27ac-dependent DNA looping data were generated to identify 7,531 cell type-specific CREs across 15 normal human cell types. A co-enrichment framework nominated 838 cell type-specific, recurrent heterotypic DNA motif combinations (DMCs), which were functionally validated using massively parallel reporter assays. Compared to their normal counterparts, cancer cells induced DMCs linked to neoplasia-enabling processes that operate in normal cells while also engaging entirely new DMCs. These data identify a cis-regulatory combinatorial DNA motif lexicon for cell type-specific gene regulation in diverse normal and diseased human cells. Purpose: To identify a cis-regulatory combinatorial DNA motif lexicon mediating cell type-specific gene regulation in diverse normal and diseased human cells, matched RNA-seq, chromatin accessibility profiling via ATAC-seq, and enhancer-promoter looping via H3K27ac HiChIP was performed in 15 primary human cell types and 6 human cancer cell lines. Processed and raw data for all cell types can be found in this repository. Squamous cell carcinoma cell line raw and processed data can be found at Jung, et al. "XXX". All biological replicates (n=2) are merged.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE188403 | GEO | 2022/08/17

REPOSITORIES: GEO