Set4 coordinates the activity of histone deacetylases and regulates stress-responsive gene expression within subtelomeric regions in yeast

Abstract

The yeast chromatin protein Set4 is a member of the Set3-subfamily of SET domain proteins which play critical roles in the regulation of gene expression in diverse developmental and environmental contexts, although they appear to lack methyltransferase activity. The molecular functions of Set4 are relatively unexplored, likely due to its low abundance in standard growth conditions. We previously reported that Set4 promotes survival during oxidative stress and regulates expression of stress response genes via stress-dependent chromatin localization. In this study, global gene expression analysis and investigation of histone modification status has revealed a role for Set4 in maintaining gene repressive mechanisms within yeast subtelomeres under both normal and stress conditions. We show that Set4 works in a partially overlapping pathway to the SIR complex and the histone deacetylase Rpd3 to maintain proper levels of histone acetylation and expression of stress response genes encoded in subtelomeres. This role for Set4 is particularly critical for cells under hypoxic conditions, and the loss of Set4 decreases cell fitness and cell wall integrity in hypoxia. These findings uncover a new regulator of subtelomeric chromatin that is key to stress defense pathways and demonstrate a function for yeast Set4 in regulating repressive, heterochromatin-like environments.

Identification of Novel Gene variants for Autism Spectrum Disorder in an Indian Patient using Whole Exome Sequencing

“…SETD5 is located on chromosome 3p25.3 and encodes the SETD5 protein composed of 1442 amino acids [39], and consists of 31 exons and is ubiquitously expressed in human tissues such as the brain, thyroid, skin, ovary, lung and endometrium [40,41]. SETD5 contains a SET domain and is thus annotated as a candidate protein of lysine methyltransferase, which methylates H3K36 up to the tri-methyl form (H3K36me3) [40,42,43…”