A comparative analysis of Smad-responsive motifs identifies multiple regulatory inputs for TGF-β transcriptional activation.

ChIP-sequencing (ChIP-seq) DNA-binding protein SMAD transcription factor signal transduction transcription factor transcription regulation transforming growth factor β (TGF-β)

Journal

The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R

Informations de publication

Date de publication:
18 10 2019
Historique:
received: 21 06 2019
revised: 29 08 2019
pubmed: 5 9 2019
medline: 23 6 2020
entrez: 5 9 2019
Statut: ppublish

Résumé

Smad proteins are transcriptional regulators activated by TGF-β. They are known to bind to two distinct Smad-responsive motifs, namely the Smad-binding element (SBE) (5'-GTCTAGAC-3') and CAGA motifs (5'-AGCCAGACA-3' or 5'-TGTCTGGCT-3'). However, the mechanisms by which these motifs promote Smad activity are not fully elucidated. In this study, we performed DNA CASTing, binding assays, ChIP sequencing, and quantitative RT-PCR to dissect the details of Smad binding and function of the SBE and CAGA motifs. We observed a preference for Smad3 to bind CAGA motifs and Smad4 to bind SBE, and that either one SBE or a triple-CAGA motif forms a

Identifiants

pubmed: 31481467
pii: S0021-9258(20)33787-X
doi: 10.1074/jbc.RA119.009877
pmc: PMC6802517
doi:

Substances chimiques

SMAD2 protein, human 0
SMAD3 protein, human 0
SMAD4 protein, human 0
Smad2 Protein 0
Smad3 Protein 0
Smad4 Protein 0
Transforming Growth Factor beta 0

Types de publication

Comparative Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

15466-15479

Informations de copyright

© 2019 Itoh et al.

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Auteurs

Yuka Itoh (Y)

Department of Biochemistry, Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.

Daizo Koinuma (D)

Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.

Chiho Omata (C)

Department of Biochemistry, Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.

Tomohiro Ogami (T)

Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.

Mitsuyoshi Motizuki (M)

Department of Biochemistry, Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.

So-Ichi Yaguchi (SI)

Department of Biochemistry, Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.

Takuma Itoh (T)

Department of Biochemistry, Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
Research Training Program for Undergraduates, Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.

Kunio Miyake (K)

Department of Social Medicine, Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.

Shuichi Tsutsumi (S)

Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.

Hiroyuki Aburatani (H)

Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.

Masao Saitoh (M)

Department of Biochemistry, Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
Center for Medical Education and Science, Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.

Kohei Miyazono (K)

Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.

Keiji Miyazawa (K)

Department of Biochemistry, Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan kmiyazawa@yamanashi.ac.jp.

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Classifications MeSH