Identification of genetic networks interacting with COUP-TF II to determinate the atrial cardiac cells identity by the SMyHC III promoter

• Grant number: 15/12549-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2015
• End date: January 31, 2020
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: José Xavier Neto
• Grantee: Luana Nunes Santos
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Campinas , SP, Brazil
• Associated scholarship(s): 18/09839-7 - Atrial selectivity from a complex nuclear receptor driven by androgen receptor: a novel gene regulatory network, BE.EP.DD

Abstract

The cardiac development is a complex process with different pathways. In this project we intent to validate protein-protein interactions that were identified by mass spectrometry and that are likely related to the development of the heart inflow tract (sinus venosus and atrium). Previously, our group identified regulatory elements, controlling atrial-specific expression of SMyHC III promoter (Slow Myosin Heavy Chain III), contained within a Complex Nuclear Receptor Responsive Element (ECRRN). The ECRRN is a 33 base pairs (bp), purine-rich (A/G) sequence, containing putative binding sites for nuclear receptor transcription factors. One of the best characterized nuclear receptors is the orphan nuclear receptor COUP-TF II (Chicken Ovalbumin Promoter-Transcription Factor II), playing pivotal roles in many biological processes, such as angiogenesis and atrial development. In cell transactivation assays COUP-TF II has been shown to activate the SMyHC III promoter. Experiments overexpressing COUP-TF II in HEK293T cells, followed by immunoprecipitation and mass spectrometry analysis, suggest that several proteins, immunoprecipitated with COUP-TF II, are known to interact with Glucocorticoid Receptor (GR), Androgen Receptor (AR) and p53. Our preliminary results suggest a new concept to understand the atrial-specific regulation whereby specificity lays mainly through protein-protein interactions between nuclear receptors and, possibly, corregulators. Then, our aim in this project is to elucidate the COUP-TF II interaction with these receptors and nuclear corregulators and identify new factors in the regulatory pathways driving the atrial-specific expression of SMyHC III promoter during the development of the heart inflow tract. (AU)

Scientific publications

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

SANTOS, LUANA NUNES; COSTA, ANGELA MARIA SOUSA; NIKOLOV, MARTIN; CARVALHO, JOAO E.; SAMPAIO, ALLYSSON COELHO; STOCKDALE, FRANK E.; WANG, GANG FENG; CASTILLO, HOZANA ANDRADE; GRIZANTE, MARIANA BORTOLETTO; DUDCZIG, STEFANIE; et al. Unraveling the evolutionary origin of the complex Nuclear Receptor Element (cNRE), a cis-regulatory module required for preferential expression in the atrial chamber. COMMUNICATIONS BIOLOGY, v. 7, n. 1, p. 15-pg., 2024-04-04. (18/09839-7, 15/12549-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SANTOS, Luana Nunes. Genetic network interacting with COUPTF-II to determine the atrial identity through the complex nuclear receptor element (cNRE).. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.