Validation of response elements for the nuclear receptors COUP-TFII in the SMyHC3 gene promoter

• Grant number: 11/23725-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): June 01, 2012
• Effective date (End): December 31, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Ana Carolina Migliorini Figueira
• Grantee: Juliana Fattori
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil

Abstract

Nuclear receptors comprise a large family of transcription factors that are activated by ligands. These receptors are potent regulators of cell development and differentiation, and organ physiology. Their function is to regulate gene transcription by binding specific DNA sequences called hormone response elements (HREs). Within this large family of proteins are the "orphan" receptors, such as COUP-TFI and II, for which no ligand has been identified so far. Currently, it is known that the receptor COUP-TFII exhibits various types of HREs binding partners. However, DR1 (direct repeat separated by one base pair) is the preferred and most common element in gene promoters influenced by COUP-TFII. In mammals, this nuclear receptor regulates many biological processes, such as angiogenesis, neural development, organogenesis, cell determination, metabolic homeostasis, cicardian rhythm and cardiac development. Furthermore, it was observed that COUP-TFII is also involved in atrial specification. However, this latter role is not well established and it is also unclear how the receptor is regulated by ligands. In order to better understand the molecular basis of the COUP-TFII functioning and regulation in a promoter region very important for cardiac development, this project aims to characterize the interaction between COUP-TFII and the atrial gene promoter SMyHC3. This particular research makes part of a larger project, which aims to study the cardiac patterning. In addition, this cardiac process, which is regulated by retinoic acid, also appears to be regulated by other proteins, such as the orphan nuclear receptor COUP-TFII. Indeed, COUP-TFII, according to previous studies, might be involved in the regulation of the promoter SMyHC3 by retinoic acid.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FATTORI, JULIANA; CAMPOS, JESSICA L. O.; DORATIOTO, TABATA R.; ASSIS, LUCAS M.; VITORINO, MARIELA T.; POLIKARPOV, IGOR; XAVIER-NETO, JOSE; FIGUEIRA, ANA CAROLINA M.. RXR Agonist Modulates TR: Corepressor Dissociation Upon 9-cis Retinoic Acid Treatment. MOLECULAR ENDOCRINOLOGY, v. 29, n. 2, p. 258-273, FEB 2015. (10/17048-8, 11/23725-5, 13/08743-2, 11/23659-2)