RESUMO
Apoptosis-inducing factor 1 (AIF1) overexpression is intimately linked to the sensitivity of yeast cells towards hydrogen peroxide or acetic acid. Therefore, studying the mechanism of AIF1 regulation in the cell would provide a significant understanding of the factors guiding yeast apoptosis. In this report, we show the time-dependent induction of AIF1 under hydrogen peroxide stress. Additionally, we find that AIF1 expression in response to hydrogen peroxide is mediated by two transcription factors, Yap5 (DNA binding) and Cdc73 (non-DNA binding). Furthermore, substituting the H3K36 residue with another amino acid significantly abrogates AIF1 expression. However, substituting the lysine (K) in H3K4 or H3K79 with alanine (A) does not affect AIF1 expression level under hydrogen peroxide stress. Altogether, reduced AIF1 expression in cdc73Δ is plausibly due to reduced H3K36me3 levels in the cells.
Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Fator de Indução de Apoptose/genética , Fator de Indução de Apoptose/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Metilação , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The field of genetics has expanded a lot in the past few decades due to the accessibility of human genome sequences, but still, the regulation of transcription cannot be explicated exclusively by the sequence of DNA of an individual. The coordination and crosstalk between chromatin factors which are conserved is indispensable for all living creatures. The regulation of gene expression has been dependent on the methylation of DNA, post-translational modifications of histones, effector proteins, chromatin remodeler enzymes that affect the chromatin structure and function, and other cellular activities such as DNA replication, DNA repair, proliferation and growth. The mutation and deletion of these factors can lead to human diseases. Various studies are being performed to identify and understand the gene regulatory mechanisms in the diseased state. The information from these high throughput screening studies is able to aid the treatment developments based on the epigenetics regulatory mechanisms. This book chapter will discourse on various modifications and their mechanisms that take place on histones and DNA that regulate the transcription of genes.
