Nonlinear transcriptional responses to gradual modulation of transcription factor dosage.

ABSTRACT: Genomic loci associated with common traits and diseases are typically non-coding and likely impact gene expression, sometimes coinciding with rare loss-of-function variants in the target gene. However, our understanding of how gradual changes in gene dosage affect molecular, cellular, and organismal traits is currently limited. To address this gap, we induced gradual changes in gene expression of four genes using CRISPR activation and inactivation. Downstream transcriptional consequences of dosage modulation of three master trans-regulators associated with blood cell traits (GFI1B, NFE2, and MYB) were examined using targeted single-cell multimodal sequencing. We showed that guide tiling around the TSS is the most effective way to modulate cis gene expression acr

SUBMITTER: Domingo J 

PROVIDER: S-EPMC10925300 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature