Fluid shear stress-modulated chromatin accessibility reveals the mechano-dependency of endothelial SMAD1/5-mediated gene transcription.

Biological sciences Molecular biology Molecular interaction

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
15 Sep 2023
Historique:
received: 16 11 2022
revised: 20 04 2023
accepted: 12 07 2023
medline: 8 9 2023
pubmed: 8 9 2023
entrez: 8 9 2023
Statut: epublish

Résumé

Bone morphogenetic protein (BMP) signaling and fluid shear stress (FSS) mediate complementary functions in vascular homeostasis and disease development. It remains to be shown whether altered chromatin accessibility downstream of BMP and FSS offers a crosstalk level to explain changes in SMAD-dependent transcription. Here, we employed ATAC-seq to analyze arterial endothelial cells stimulated with BMP9 and/or FSS. We found that BMP9-sensitive regions harbor non-palindromic GC-rich SMAD-binding elements (GGCTCC) and 69.7% of these regions become BMP-insensitive in the presence of FSS. While GATA and KLF transcription factor (TF) motifs are unique to BMP9- and FSS-sensitive regions, respectively, SOX motifs are common to both. Finally, we show that both SOX(13/18) and GATA(2/3/6) family members are directly upregulated by SMAD1/5. These findings highlight the mechano-dependency of SMAD-signaling by a sequential mechanism of first elevated pioneer TF expression, allowing subsequent chromatin opening to eventually providing accessibility to novel SMAD binding sites.

Identifiants

pubmed: 37680470
doi: 10.1016/j.isci.2023.107405
pii: S2589-0042(23)01482-7
pmc: PMC10481294
doi:

Types de publication

Journal Article

Langues

eng

Pagination

107405

Informations de copyright

© 2023.

Déclaration de conflit d'intérêts

The authors declare no competing interest.

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Auteurs

Jerome Jatzlau (J)

Institute of Chemistry and Biochemistry - Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Berlin-Brandenburg School for Regenerative Therapies (BSRT), 13353 Berlin, Germany.
Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.

Paul-Lennard Mendez (PL)

Institute of Chemistry and Biochemistry - Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
International Max-Planck Research School for Biology AND Computation (IMPRS-BAC), 14195 Berlin, Germany.

Aybuge Altay (A)

Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.

Lion Raaz (L)

Institute of Chemistry and Biochemistry - Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
International Max-Planck Research School for Biology AND Computation (IMPRS-BAC), 14195 Berlin, Germany.
Institute of Medical and Human Genetics, Charité Universitätsmedizin, 13353 Berlin, Germany.

Yufei Zhang (Y)

Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.

Sophia Mähr (S)

Institute of Chemistry and Biochemistry - Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.

Akin Sesver (A)

Institute of Chemistry and Biochemistry - Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.

Maria Reichenbach (M)

Institute of Chemistry and Biochemistry - Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.

Stefan Mundlos (S)

Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
International Max-Planck Research School for Biology AND Computation (IMPRS-BAC), 14195 Berlin, Germany.
Institute of Medical and Human Genetics, Charité Universitätsmedizin, 13353 Berlin, Germany.

Martin Vingron (M)

Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
International Max-Planck Research School for Biology AND Computation (IMPRS-BAC), 14195 Berlin, Germany.

Petra Knaus (P)

Institute of Chemistry and Biochemistry - Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Berlin-Brandenburg School for Regenerative Therapies (BSRT), 13353 Berlin, Germany.
International Max-Planck Research School for Biology AND Computation (IMPRS-BAC), 14195 Berlin, Germany.

Classifications MeSH