Complementary strategies for directing in vivo transcription factor binding through DNA binding domains and intrinsically disordered regions

Divya Krishna Kumar, Felix Jonas, Tamar Jana, Sagie Brodsky, Miri Carmi, Naama Barkai

Research output: Contribution to journalArticlepeer-review

Abstract

DNA binding domains (DBDs) of transcription factors (TFs) recognize DNA sequence motifs that are highly abundant in genomes. Within cells, TFs bind a subset of motif-containing sites as directed by either their DBDs or DBD-external (nonDBD) sequences. To define the relative roles of DBDs and nonDBDs in directing binding preferences, we compared the genome-wide binding of 48 (∼30%) budding yeast TFs with their DBD-only, nonDBD-truncated, and nonDBD-only mutants. With a few exceptions, binding locations differed between DBDs and TFs, resulting from the cumulative action of multiple determinants mapped mostly to disordered nonDBD regions. Furthermore, TFs’ preferences for promoters of the fuzzy nucleosome architecture were lost in DBD-only mutants, whose binding spread across promoters, implicating nonDBDs’ preferences in this hallmark of budding yeast regulatory design. We conclude that DBDs and nonDBDs employ complementary DNA-targeting strategies, whose balance defines TF binding specificity along genomes.

Original languageEnglish
Pages (from-to)1462-1473.e5
Number of pages18
JournalMolecular Cell
Volume83
Issue number9
DOIs
StatePublished - 4 May 2023

Fingerprint

Dive into the research topics of 'Complementary strategies for directing in vivo transcription factor binding through DNA binding domains and intrinsically disordered regions'. Together they form a unique fingerprint.

Cite this