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Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment

A critical but molecularly uncharacterized step in heart formation and regeneration is the process that commits progenitor cells to differentiate into cardiomyocytes. Here, we show that the endoderm-derived dual Nodal/bone morphogenetic protein (BMP) antagonist Cerberus-1 (Cer1) in embryonic stem ce...

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Autores principales: Cai, Wenqing, Albini, Sonia, Wei, Ke, Willems, Erik, Guzzo, Rosa M., Tsuda, Masanao, Giordani, Lorenzo, Spiering, Sean, Kurian, Leo, Yeo, Gene W., Puri, Pier Lorenzo, Mercola, Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828519/
https://www.ncbi.nlm.nih.gov/pubmed/24186978
http://dx.doi.org/10.1101/gad.225144.113
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author Cai, Wenqing
Albini, Sonia
Wei, Ke
Willems, Erik
Guzzo, Rosa M.
Tsuda, Masanao
Giordani, Lorenzo
Spiering, Sean
Kurian, Leo
Yeo, Gene W.
Puri, Pier Lorenzo
Mercola, Mark
author_facet Cai, Wenqing
Albini, Sonia
Wei, Ke
Willems, Erik
Guzzo, Rosa M.
Tsuda, Masanao
Giordani, Lorenzo
Spiering, Sean
Kurian, Leo
Yeo, Gene W.
Puri, Pier Lorenzo
Mercola, Mark
author_sort Cai, Wenqing
collection PubMed
description A critical but molecularly uncharacterized step in heart formation and regeneration is the process that commits progenitor cells to differentiate into cardiomyocytes. Here, we show that the endoderm-derived dual Nodal/bone morphogenetic protein (BMP) antagonist Cerberus-1 (Cer1) in embryonic stem cell cultures orchestrates two signaling pathways that direct the SWI/SNF chromatin remodeling complex to cardiomyogenic loci in multipotent (KDR/Flk1(+)) progenitors, activating lineage-specific transcription. Transient inhibition of Nodal by Cer1 induces Brahma-associated factor 60c (Baf60c), one of three Baf60 variants (a, b, and c) that are mutually exclusively assembled into SWI/SNF. Blocking Nodal and BMP also induces lineage-specific transcription factors Gata4 and Tbx5, which interact with Baf60c. siRNA to Cer1, Baf60c, or the catalytic SWI/SNF subunit Brg1 prevented the developmental opening of chromatin surrounding the Nkx2.5 early cardiac enhancer and cardiomyocyte differentiation. Overexpression of Baf60c fully rescued these deficits, positioning Baf60c and SWI/SNF function downstream from Cer1. Thus, antagonism of Nodal and BMP coordinates induction of the myogenic Baf60c variant and interacting transcription factors to program the developmental opening of cardiomyocyte-specific loci in chromatin. This is the first demonstration that cues from the progenitor cell environment direct the subunit variant composition of SWI/SNF to remodel the transcriptional landscape for lineage-specific differentiation.
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spelling pubmed-38285192014-05-01 Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment Cai, Wenqing Albini, Sonia Wei, Ke Willems, Erik Guzzo, Rosa M. Tsuda, Masanao Giordani, Lorenzo Spiering, Sean Kurian, Leo Yeo, Gene W. Puri, Pier Lorenzo Mercola, Mark Genes Dev Research Paper A critical but molecularly uncharacterized step in heart formation and regeneration is the process that commits progenitor cells to differentiate into cardiomyocytes. Here, we show that the endoderm-derived dual Nodal/bone morphogenetic protein (BMP) antagonist Cerberus-1 (Cer1) in embryonic stem cell cultures orchestrates two signaling pathways that direct the SWI/SNF chromatin remodeling complex to cardiomyogenic loci in multipotent (KDR/Flk1(+)) progenitors, activating lineage-specific transcription. Transient inhibition of Nodal by Cer1 induces Brahma-associated factor 60c (Baf60c), one of three Baf60 variants (a, b, and c) that are mutually exclusively assembled into SWI/SNF. Blocking Nodal and BMP also induces lineage-specific transcription factors Gata4 and Tbx5, which interact with Baf60c. siRNA to Cer1, Baf60c, or the catalytic SWI/SNF subunit Brg1 prevented the developmental opening of chromatin surrounding the Nkx2.5 early cardiac enhancer and cardiomyocyte differentiation. Overexpression of Baf60c fully rescued these deficits, positioning Baf60c and SWI/SNF function downstream from Cer1. Thus, antagonism of Nodal and BMP coordinates induction of the myogenic Baf60c variant and interacting transcription factors to program the developmental opening of cardiomyocyte-specific loci in chromatin. This is the first demonstration that cues from the progenitor cell environment direct the subunit variant composition of SWI/SNF to remodel the transcriptional landscape for lineage-specific differentiation. Cold Spring Harbor Laboratory Press 2013-11-01 /pmc/articles/PMC3828519/ /pubmed/24186978 http://dx.doi.org/10.1101/gad.225144.113 Text en © 2013 Cai et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
spellingShingle Research Paper
Cai, Wenqing
Albini, Sonia
Wei, Ke
Willems, Erik
Guzzo, Rosa M.
Tsuda, Masanao
Giordani, Lorenzo
Spiering, Sean
Kurian, Leo
Yeo, Gene W.
Puri, Pier Lorenzo
Mercola, Mark
Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment
title Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment
title_full Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment
title_fullStr Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment
title_full_unstemmed Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment
title_short Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment
title_sort coordinate nodal and bmp inhibition directs baf60c-dependent cardiomyocyte commitment
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828519/
https://www.ncbi.nlm.nih.gov/pubmed/24186978
http://dx.doi.org/10.1101/gad.225144.113
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