Rare but specific: 5-bp composite motifs define SMAD binding in BMP signaling.

ABSTRACT:

Background

Receptor-activated SMADs trimerize with SMAD4 to regulate context-dependent target gene expression. However, the presence of a single SMAD1/5/8 binding motif in cis-regulatory elements alone does not trigger transcription in native contexts. We hypothesize that binding to composite motifs in which at least two SMAD binding sites are in close proximity would be enough to induce transcription as this scenario allows the simultaneous interaction of at least two SMAD proteins, thereby increasing specificity and affinity.

Results

Using more than 65 distinct firefly luciferase constructs, we delineated the minimal requirements for BMP-induced gene activation. We propose a model in which two SMAD-MH1 domains bind a SMAD-composite motif in a back-to-back fashion with a 5-

SUBMITTER: Jatzlau J 

PROVIDER: S-EPMC11907993 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature