Unraveling the evolutionary origin of the complex Nuclear Receptor Element (cNRE), a cis-regulatory module required for preferential expression in the atrial chamber
Year: 2024
Type: article
Abstract: Cardiac function requires appropriate proteins in each chamber. Atria requires slow myosin to act as reservoirs, while ventricles demand fast myosin for swift pumping. Myosins are thus under chamber-biased cis -regulation, with myosin gene expression imbalances leading to congenital heart dysfunction. To identify regulatory inputs leading to cardiac chamber-biased expression, we computationally and molecularly dissected the quail Slow Myosin Heavy Chain III ( SMyHC III ) promoter that drives preferential expression to the atria. We show that SMyHC III gene states are orchestrated by a complex Nuclear Receptor Element (cNRE) of 32 base pairs. Using transgenesis in zebrafish and mice, we demonstrate that preferential atrial expression is achieved by a combinatorial regulatory input composed of atrial activation motifs and ventricular repression motifs. Using comparative genomics, we show that the cNRE might have emerged from an endogenous viral element through infection of an ancestral host germline, revealing an evolutionary pathway to cardiac chamber-specific expression.
Source: Communications Biology
Authors: Luana Nunes Santos, Ângela Maria Sousa Costa, Martin Nikolov, João E. Carvalho, Allysson Coelho Sampaio, Frank E. Stockdale, Gang Feng Wang, Hozana Andrade Castillo, Mariana Bortoletto Grizante, Stefanie Dudczig, Michelle Vasconcelos, Nadia Rosenthal, Patricia Regina Jusuf, Hieu T. Nim, Paulo de Oliveira, Tatiana Guimarães de Freitas Matos, William Nikovits, Izabella Luisa Tambones, Ana Carolina Migliorini Figueira, Michael Schubert, Mirana Ramialison, José Xavier-Neto
Institutions: Universidade de São Paulo, Australian Regenerative Medicine Institute, Brazilian Center for Research in Energy and Materials, Brazilian Biosciences National Laboratory, Monash University, Centre National de la Recherche Scientifique, Sorbonne Université, Laboratoire de Biologie du Développement de Villefranche-sur-Mer, Institut de la Mer de Villefranche, Faculdade Santa Marcelina, Stanford Medicine, Stanford University, The University of Melbourne, Jackson Laboratory, Imperial College London, Murdoch Children's Research Institute, Universidade Federal do Ceará, Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,890
Funders: Australian Government, Agence Nationale de la Recherche, University of Melbourne, Fundação de Amparo à Pesquisa do Estado de São Paulo, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Novo Nordisk, State Government of Victoria, Centre National de la Recherche Scientifique, Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico, Novo Nordisk Fonden, Australian Research Council, National Health and Medical Research Council
OpenAlex ID: W4393948856