Massively parallel characterization of transcriptional regulatory elements.

ABSTRACT: The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states¹. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.7% of these sequences were active. By testing sequences in both orientations, we find promoters to have strand-orientation biases and their 200-nucleotide cores to function as non-cell-type-specific 'on switches' that provide

SUBMITTER: Agarwal V 

PROVIDER: S-EPMC11903340 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature