Tuning Transcription Factor Availability through Acetylation-Mediated Genomic Redistribution.

ABSTRACT: It is widely assumed that decreasing transcription factor DNA-binding affinity reduces transcription initiation by diminishing occupancy of sequence-specific regulatory elements. However, in vivo transcription factors find their binding sites while confronted with a large excess of low-affinity degenerate motifs. Here, using the melanoma lineage survival oncogene MITF as a model, we show that low-affinity binding sites act as a competitive reservoir in vivo from which transcription factors are released by mitogen-activated protein kinase (MAPK)-stimulated acetylation to promote increased occupancy of their regulatory elements. Consequently, a low-DNA-binding-affinity acetylation-mimetic MITF mutation supports melanocyte development and drives tumorigenesis, whereas a high-affinity non-acet

SUBMITTER: Louphrasitthiphol P 

PROVIDER: S-EPMC7427332 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature