Sequence discrimination by DNA-binding domain of ETS family transcription factor PU.1 is linked to specific hydration of protein-DNA interface.

ABSTRACT: PU.1 is an essential transcription factor in normal hematopoietic lineage development. It recognizes a large number of promoter sites differing only in bases flanking a core consensus of 5'-GGAA-3'. DNA binding is mediated by its ETS domain, whose sequence selectivity directly corresponds to the transactivational activity and frequency of binding sites for full-length PU.1 in vivo. To better understand the basis of sequence discrimination, we characterized its binding properties to a high affinity and low affinity site. Despite sharing a homologous structural framework as confirmed by DNase I and hydroxyl radical footprinting, the two complexes exhibit striking heterogeneity in terms of hydration properties. High affinity binding is destabilized by osmotic stress, whereas low affinity bind

SUBMITTER: Poon GM 

PROVIDER: S-EPMC3365747 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature