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

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...

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Autores: 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
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/222975
Acesso em linha:https://hdl.handle.net/2445/222975
Access Level:acceso abierto
Palavra-chave:Factors de transcripció
Expressió gènica
Transcription factors
Gene expression
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spelling Rare but specific: 5-bp composite motifs define SMAD binding in BMP signalingJatzlau, JeromeDo, Sophie-NhiMees, Rebeca AngeliqueMendez, Paul LennardKhan, Rameez JabeerMaas, LukasRuiz Sainz, LidiaMartín Malpartida, PauMacías Hernández, María J.Knaus, PetraFactors de transcripcióExpressió gènicaTranscription factorsGene expressionBackgroundReceptor-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.BioMed Central2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/222975Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s12915-025-02183-1Bmc Biology, 2025, vol. 23, 79https://doi.org/10.1186/s12915-025-02183-1cc-by (c) Jatzlau, Jerome et al., 2025http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2229752026-05-27T06:46:51Z
dc.title.none.fl_str_mv Rare but specific: 5-bp composite motifs define SMAD binding in BMP signaling
title Rare but specific: 5-bp composite motifs define SMAD binding in BMP signaling
spellingShingle Rare but specific: 5-bp composite motifs define SMAD binding in BMP signaling
Jatzlau, Jerome
Factors de transcripció
Expressió gènica
Transcription factors
Gene expression
title_short Rare but specific: 5-bp composite motifs define SMAD binding in BMP signaling
title_full Rare but specific: 5-bp composite motifs define SMAD binding in BMP signaling
title_fullStr Rare but specific: 5-bp composite motifs define SMAD binding in BMP signaling
title_full_unstemmed Rare but specific: 5-bp composite motifs define SMAD binding in BMP signaling
title_sort Rare but specific: 5-bp composite motifs define SMAD binding in BMP signaling
dc.creator.none.fl_str_mv 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
author Jatzlau, Jerome
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Factors de transcripció
Expressió gènica
Transcription factors
Gene expression
topic Factors de transcripció
Expressió gènica
Transcription factors
Gene expression
description 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.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/222975
url https://hdl.handle.net/2445/222975
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s12915-025-02183-1
Bmc Biology, 2025, vol. 23, 79
https://doi.org/10.1186/s12915-025-02183-1
dc.rights.none.fl_str_mv cc-by (c) Jatzlau, Jerome et al., 2025
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Jatzlau, Jerome et al., 2025
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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