puc-header

BMP9 and Fluid Shear Stress Regulate Endothelial Chromatin Accessibility and Expression of SMAD Low Affinity Target Genes

35 Pages Posted: 6 Dec 2022 Publication Status: Published

See all articles by Jerome Jatzlau

Jerome Jatzlau

Max Planck Society for the Advancement of the Sciences - Max Planck Institute for Molecular Genetics (MPIMG)

Paul Mendez

Max Planck Society for the Advancement of the Sciences - Max Planck Institute for Molecular Genetics (MPIMG)

Aybuge Altay

Max Planck Society for the Advancement of the Sciences - Max Planck Institute for Molecular Genetics (MPIMG)

Lion Raaz

Max Planck Society for the Advancement of the Sciences - Max Planck Institute for Molecular Genetics (MPIMG)

Yufei Zhang

Max Planck Society for the Advancement of the Sciences - Max Planck Institute for Molecular Genetics (MPIMG)

Akin Sesver

Free University of Berlin (FUB) - Institute for Chemistry and Biochemistry

Maria Reichenbach

Free University of Berlin (FUB) - Institute for Chemistry and Biochemistry

Stefan Mundlos

Max Planck Institute for Molecular Genetics

Martin Vingron

Max Planck Society for the Advancement of the Sciences - The Department of Computational Molecular Biology

Petra Knaus

Free University of Berlin (FUB) - Institute for Chemistry and Biochemistry

More...

Abstract

Bone morphogenetic protein (BMP) signaling and fluid shear stress (FSS) together modulate vascular homeostasis and disease development. Both induce a wide range of target genes, independent of each other but also in a co- or anti-regulatory manner. Here, we applied assay for transposase accessible chromatin followed by sequencing (ATAC-seq) on BMP9 and FSS stimulated arterial endothelial cells and identified broad changes in chromatin accessibility which are unique or shared between both stimuli. BMP9-sensitive regions harbor SMAD-binding elements, characteristic of SMAD low-affinity target genes, i.e., genes only induced by high levels of phosphorylated SMAD1/5. Upon combination with FSS, 69.7% of those BMP9-sensitive regions, become insensitive to BMP9, highlighting the context dependency of SMAD signaling. Motif enrichment and footprint analysis further identified SOX, BACH and AP1 transcription factor family members as regulators of regions sensitive to both BMP9 and FSS. Our study provides new insights in the complex regulation of BMP9 and FSS mediated target gene regulation and establishes a new method to analyze SMAD low-affinity target genes which can easily be adapted to studies on other transcription factors.

Note:

Funding Information: J.J. was supported by Einstein Center for Regenerative Therapies (ECRT). P.K. acknowledges the support from ECRT, DFG (SFB1444), and Morbus Osler Society. P.-L. Mendez and L. Raaz were supported by IMPRS-BAC.

Declaration of Interests: The authors declare no competing interest.

Keywords: BMP, Fluid shear stress, SMAD1/5/8, target gene regulation, ATAC-Seq

Suggested Citation

Jatzlau, Jerome and Mendez, Paul and Altay, Aybuge and Raaz, Lion and Zhang, Yufei and Sesver, Akin and Reichenbach, Maria and Mundlos, Stefan and Vingron, Martin and Knaus, Petra, BMP9 and Fluid Shear Stress Regulate Endothelial Chromatin Accessibility and Expression of SMAD Low Affinity Target Genes. Available at SSRN: https://ssrn.com/abstract=4290059 or http://dx.doi.org/10.2139/ssrn.4290059
This version of the paper has not been formally peer reviewed.

Jerome Jatzlau

Max Planck Society for the Advancement of the Sciences - Max Planck Institute for Molecular Genetics (MPIMG) ( email )

Paul Mendez

Max Planck Society for the Advancement of the Sciences - Max Planck Institute for Molecular Genetics (MPIMG)

Aybuge Altay

Max Planck Society for the Advancement of the Sciences - Max Planck Institute for Molecular Genetics (MPIMG) ( email )

Lion Raaz

Max Planck Society for the Advancement of the Sciences - Max Planck Institute for Molecular Genetics (MPIMG) ( email )

Yufei Zhang

Max Planck Society for the Advancement of the Sciences - Max Planck Institute for Molecular Genetics (MPIMG) ( email )

Akin Sesver

Free University of Berlin (FUB) - Institute for Chemistry and Biochemistry ( email )

Maria Reichenbach

Free University of Berlin (FUB) - Institute for Chemistry and Biochemistry ( email )

Stefan Mundlos

Max Planck Institute for Molecular Genetics ( email )

Ihnestraße 63-73
Berlin, 14195
Germany

Martin Vingron

Max Planck Society for the Advancement of the Sciences - The Department of Computational Molecular Biology ( email )

Berlin
Germany

Petra Knaus (Contact Author)

Free University of Berlin (FUB) - Institute for Chemistry and Biochemistry ( email )

Click here to go to Cell.com

Paper statistics

Downloads
16
Abstract Views
303
PlumX Metrics