Analysis of the role of the gene H3F3B in the maintenance of the X-chromosome inactivation

• Grant number: 18/20548-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2019
• End date: July 31, 2020
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Lygia da Veiga Pereira
• Grantee: Daniel Minatti Felismino
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The X-chromosome inactivation (XCI) consists in the silencing of one of the X chromosomes of females, and it acts as an important mechanism of genic dosage compensation, preventing that the transcripts of genes located on that chromosome get produced twice as much in females than in males. The X silencing involves several chromatin modifications, that culminates in the formation of facultative heterochromatin, which is maintained through the subsequent cell divisions. This maintenance of XCI process is a constant target of studies and researches, however specific epigenetic issues, such as the action mechanisms and the identity of factors related to this process, remain poorly known and understood. Our laboratory did a functional genomic trial using shRNAs (short-hairpin RNAs) libraries to find genes that are involved in the maintenance of the XCI in humans and, afterwards, analyzed the several candidates based on the literature and in experiments, in order to reduce that list to few candidates, which would be more probably related to the process in hand. This project's proposal is to evaluate the role of one of those candidates, the H3F3B gene, in the maintenance of the X-chromosome inactivation.