SMYD5 is a Regulator of the Mild Hypothermia Response

Overview

Journal bioRxiv

Date 2023 Jun 19

PMID 37333301

Authors

Salvor Rafnsdottir

Kijin Jang

Sara Tholl Halldorsdottir

Meghna Vinod

Arnhildur Tomasdottir

Katrin Moller

Katrin Halldorsdottir

Tinna Reynisdottir

Laufey Halla Atladottir

Kristin Elisabet Allison

Kevin Ostacolo

Jin He

Li Zhang

Frances J Northington

Erna Magnusdottir

Raul Chavez-Valdez

Kimberley Jade Anderson

Hans Tomas Bjornsson

Affiliations

Soon will be listed here.

Abstract

The mild hypothermia response (MHR) maintains organismal homeostasis during cold exposure and is thought to be critical for the neuroprotection documented with therapeutic hypothermia. To date, little is known about the transcriptional regulation of the MHR. We utilize a forward CRISPR-Cas9 mutagenesis screen to identify the histone lysine methyltransferase SMYD5 as a regulator of the MHR. SMYD5 represses the key MHR gene at euthermia. This repression correlates with temperature-dependent levels of H3K36me3 at the -locus and globally, indicating that the mammalian MHR is regulated at the level of histone modifications. We have identified 37 additional SMYD5 regulated temperature-dependent genes, suggesting a broader MHR-related role for SMYD5. Our study provides an example of how histone modifications integrate environmental cues into the genetic circuitry of mammalian cells and provides insights that may yield therapeutic avenues for neuroprotection after catastrophic events.

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