Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/222975
Title: Rare but specific: 5-bp composite motifs define SMAD binding in BMP signaling
Author: Jatzlau, Jerome
Do, Sophie-Nhi
Mees, Rebeca Angelique
Mendez, Paul Lennard
Khan, Rameez Jabeer
Maas, Lukas
Ruiz Sainz, Lidia
Martín Malpartida, Pau
Macías Hernández, María J.
Knaus, Petra
Keywords: Factors de transcripció
Expressió gènica
Transcription factors
Gene expression
Issue Date: 13-Mar-2025
Publisher: BioMed Central
Abstract: BackgroundReceptor-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.ResultsUsing 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-bp distance between the SMAD-motifs on opposing DNA strands. However screening of SMAD1-bound regions across a variety of cell types highlights that these composite motifs are extremely uncommon, explaining below 1% of SMAD1 binding events.ConclusionsDeviations from these minimal requirements prevent transcription and underline the need for co-transcription factors to achieve gene activation.
Note: Reproducció del document publicat a: https://doi.org/10.1186/s12915-025-02183-1
It is part of: Bmc Biology, 2025, vol. 23, 79
URI: https://hdl.handle.net/2445/222975
Related resource: https://doi.org/10.1186/s12915-025-02183-1
ISSN: 1741-7007
Appears in Collections:Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

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