A role for pH dynamics regulating transcription factor DNA-binding selectivity.

ABSTRACT: Intracellular pH (pHi) dynamics regulates diverse cell processes such as proliferation, dysplasia, and differentiation, often mediated by the protonation state of a functionally critical histidine residue in endogenous pH sensing proteins. How pHi dynamics can directly regulate gene expression or whether transcription factors can function as pH sensors has received limited attention. We tested the prediction that transcription factors with a histidine in their DNA-binding domain (DBD) that forms hydrogen bonds with nucleotides can have pH-regulated activity, which is relevant to more than 85 transcription factors in distinct families, including FOX, KLF, SOX, and MITF/Myc. Focusing on FOX family transcription factors, we use unbiased SELEX-seq to identify pH-dependent DNA-binding motif pre

SUBMITTER: Kisor KP 

PROVIDER: S-EPMC12135187 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature