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ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif

Dysregulated bone morphogenetic protein (BMP) signaling in endothelial cells (ECs) and pulmonary arterial smooth muscle cells (PASMCs) are implicated in human genetic disorders. Here, we generated genome-wide maps of Smad1/5 binding sites in ECs and PASMCs. Smad1/5 preferentially bound to the region...

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Autores principales: Morikawa, Masato, Koinuma, Daizo, Tsutsumi, Shuichi, Vasilaki, Eleftheria, Kanki, Yasuharu, Heldin, Carl-Henrik, Aburatani, Hiroyuki, Miyazono, Kohei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203580/
https://www.ncbi.nlm.nih.gov/pubmed/21764776
http://dx.doi.org/10.1093/nar/gkr572
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author Morikawa, Masato
Koinuma, Daizo
Tsutsumi, Shuichi
Vasilaki, Eleftheria
Kanki, Yasuharu
Heldin, Carl-Henrik
Aburatani, Hiroyuki
Miyazono, Kohei
author_facet Morikawa, Masato
Koinuma, Daizo
Tsutsumi, Shuichi
Vasilaki, Eleftheria
Kanki, Yasuharu
Heldin, Carl-Henrik
Aburatani, Hiroyuki
Miyazono, Kohei
author_sort Morikawa, Masato
collection PubMed
description Dysregulated bone morphogenetic protein (BMP) signaling in endothelial cells (ECs) and pulmonary arterial smooth muscle cells (PASMCs) are implicated in human genetic disorders. Here, we generated genome-wide maps of Smad1/5 binding sites in ECs and PASMCs. Smad1/5 preferentially bound to the region outside the promoter of known genes, and the binding was associated with target gene upregulation. Cell-selective Smad1/5 binding patterns appear to be determined mostly by cell-specific differences in baseline chromatin accessibility patterns. We identified, for the first time, a Smad1/5 binding motif in mammals, and termed GC-rich Smad binding element (GC-SBE). Several sequences in the identified GC-SBE motif had relatively weak affinity for Smad binding, and were enriched in cell type-specific Smad1/5 binding regions. We also found that both GC-SBE and the canonical SBE affect binding affinity for the Smad complex. Furthermore, we characterized EC-specific Smad1/5 target genes and found that several Notch signaling pathway-related genes were induced by BMP in ECs. Among them, a Notch ligand, JAG1 was regulated directly by Smad1/5, transactivating Notch signaling in the neighboring cells. These results provide insights into the molecular mechanism of BMP signaling and the pathogenesis of vascular lesions of certain genetic disorders, including hereditary hemorrhagic telangiectasia.
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spelling pubmed-32035802011-10-28 ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif Morikawa, Masato Koinuma, Daizo Tsutsumi, Shuichi Vasilaki, Eleftheria Kanki, Yasuharu Heldin, Carl-Henrik Aburatani, Hiroyuki Miyazono, Kohei Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics Dysregulated bone morphogenetic protein (BMP) signaling in endothelial cells (ECs) and pulmonary arterial smooth muscle cells (PASMCs) are implicated in human genetic disorders. Here, we generated genome-wide maps of Smad1/5 binding sites in ECs and PASMCs. Smad1/5 preferentially bound to the region outside the promoter of known genes, and the binding was associated with target gene upregulation. Cell-selective Smad1/5 binding patterns appear to be determined mostly by cell-specific differences in baseline chromatin accessibility patterns. We identified, for the first time, a Smad1/5 binding motif in mammals, and termed GC-rich Smad binding element (GC-SBE). Several sequences in the identified GC-SBE motif had relatively weak affinity for Smad binding, and were enriched in cell type-specific Smad1/5 binding regions. We also found that both GC-SBE and the canonical SBE affect binding affinity for the Smad complex. Furthermore, we characterized EC-specific Smad1/5 target genes and found that several Notch signaling pathway-related genes were induced by BMP in ECs. Among them, a Notch ligand, JAG1 was regulated directly by Smad1/5, transactivating Notch signaling in the neighboring cells. These results provide insights into the molecular mechanism of BMP signaling and the pathogenesis of vascular lesions of certain genetic disorders, including hereditary hemorrhagic telangiectasia. Oxford University Press 2011-11 2011-07-15 /pmc/articles/PMC3203580/ /pubmed/21764776 http://dx.doi.org/10.1093/nar/gkr572 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene Regulation, Chromatin and Epigenetics
Morikawa, Masato
Koinuma, Daizo
Tsutsumi, Shuichi
Vasilaki, Eleftheria
Kanki, Yasuharu
Heldin, Carl-Henrik
Aburatani, Hiroyuki
Miyazono, Kohei
ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif
title ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif
title_full ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif
title_fullStr ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif
title_full_unstemmed ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif
title_short ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif
title_sort chip-seq reveals cell type-specific binding patterns of bmp-specific smads and a novel binding motif
topic Gene Regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203580/
https://www.ncbi.nlm.nih.gov/pubmed/21764776
http://dx.doi.org/10.1093/nar/gkr572
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