PT - JOURNAL ARTICLE AU - Yogita Jethmalani AU - Khoa Tran AU - Maraki Y Negesse AU - Winny Sun AU - Mark Ramos AU - Deepika Jaiswal AU - Meagan Jezek AU - Shandon Amos AU - Eric Joshua Garcia AU - DoHwan Park AU - Erin M Green TI - Set4 regulates stress response genes and coordinates histone deacetylases within yeast subtelomeres AID - 10.26508/lsa.202101126 DP - 2021 Dec 01 TA - Life Science Alliance PG - e202101126 VI - 4 IP - 12 4099 - https://www.life-science-alliance.org/content/4/12/e202101126.short 4100 - https://www.life-science-alliance.org/content/4/12/e202101126.full SO - Life Sci. Alliance2021 Dec 01; 4 AB - 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. 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 identified 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, where the loss of Set4 decreases cell fitness and cell wall integrity. These findings uncover a new regulator of subtelomeric chromatin that is key to stress defense pathways and demonstrate a function for Set4 in regulating repressive, heterochromatin-like environments.