Epigenetic-related control of neural differentiation in retinal development

• Grant number: 13/07458-2
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2013
• Effective date (End): October 31, 2017
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal researcher: Alexandre Hiroaki Kihara
• Grantee: Seyed Reza Raeisossadati
• Home Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated research grant: 08/55210-1 - Cell coupling in the arc of life: development, adaptation and degeneration of the nervous system, AP.JP

Abstract

Histone post-translational modifications are covalent modifications of histones by phosphorylation, methylation, acetylation and deacetylation, ubiquitylation, and sumoylation. Histone modifications are proposed to affect chromosome structure and function, for instance during transcription and chromatin remodeling processes. Histone lysine methylation (HKM) is an important epigenetic mechanism that regulates gene transcription activation and repression; this process directly influenced development, stem cell pluripotency, tumorigenesis, and inflammation. These lysine residues can be monomethylated, dimethylated, and trimethylated. Generally, trimethylation of lysine 4 on histone H3 (H3K4me3) is associated with activated promoters, which correlates with gene transcription. Furthermore methylation at lysine 27 on histone H3 (H3K27me) is associated with transcriptional repression in many developmental processes. Histone demethylase family may be critical to many aspects of development, since members have been found to have biologically important roles in cell cycle control and neural development through the repression of early differentiation markers. The retina begins as an early compartment of the forebrain and has frequently served as a model of CNS development. Retinal cell types are formed in a characteristic sequence from embryonic day 12 (E12) to postnatal 5 (P5) with ganglion cells, amacrine cells and horizontal cells among the early formed types and rod photoreceptors and bipolar cells formed predominantly during the later postnatal period. In this respect this study will focus on inhibition of two demethylase JMJD3 (KDM6B) and JARID1B (KDM6B) with chemical inhibitors GSK-J1 and PBIT in retina. The study will be conducted using both in vivo and in vitro approaches. Considering our prediction, we expect to observe abnormal rod photoreceptors, bipolar cells and Müller glial cells differentiation. This is the first in vivo study for inhibition of histone demethylase with chemical inhibitor in retina.

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)

RAEISOSSADATI, REZA; MOVIO, MARILIA INES; WALTER, LAIS TAKATA; TAKADA, SILVIA HONDA; DEL DEBBIO, CAROLINA BELTRAME; KIHARA, ALEXANDRE HIROAKI. Small Molecule GSK-J1 Affects Differentiation of Specific Neuronal Subtypes in Developing Rat Retina. Molecular Neurobiology, v. 56, n. 3, p. 1972-1983, MAR 2019. Web of Science Citations: 2.