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SMYD5 is a regulator of the mild hypothermia response

ABSTRACT: SMYD5 is a regulator of the mild hypothermia response

PROVIDER: PRJNA982776 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24896341.fastq.gz	Fastqsanger.gz
	SRR24896342.fastq.gz	Fastqsanger.gz
	SRR24896343.fastq.gz	Fastqsanger.gz
	SRR24895944_1.fastq.gz	Fastqsanger.gz
	SRR24895944_2.fastq.gz	Fastqsanger.gz

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SMYD5 is a regulator of the mild hypothermia response [Cut & Run]

Project description:Organisms have homeostatic mechanisms to respond to cold temperature to ensure survival including the activation of the mammalian neuroprotective mild hypothermia response (MHR) at 32°C. Utilizing a forward CRISPR-Cas9 mutagenesis screen, we identify the histone lysine methyltransferase SMYD5 as an epigenetic gatekeeper of the MHR. SMYD5 represses the key MHR gene SP1 at euthermia but not at 32°C. This repression is mirrored by temperature-dependent levels of H3K36me3 at the SP1-locus and globally indicating that the mammalian MHR is regulated at the level of histone modifications. We identified additional SMYD5-temperature dependent genes suggesting a broader MHR-related role for SMYD5. Our study provides an example of how the epigenetic machinery integrates environmental cues into the genetic circuitry of mammalian cells and suggests novel therapeutic avenues for neuroprotection after catastrophic events.

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Project description:This SuperSeries is composed of the SubSeries listed below.

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Tissue culture model of hypothermia

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Project description:Therapeutic hypothermia is a clinically effective treatment for various hypoxic and ischemic conditions, but the associated molecular mechanisms remain unclear. To gain insight into hypothermia-induced transcriptional response, mouse embryonic fibroblasts were exposed to mild hypothermia (32Â°C) or normothermia (37Â°C) for increasing time periods. We aimed to identify genes with temporally near-monotonic response as the most obvious candidates for mediating the therapeutic effects of hypothermia. Hypothermia was compared against normothermia at seven different time-points. Hypothermic and normothermic mouse embryonic fibroblasts (MEF, in 100 mm dishes, one array per time-point) were submitted to gene expression analysis using Mouse Gene 1.0 ST GeneChipÂ® (Affymetrix) microarrays. Differential gene expression analysis was performed with R package DEMI (http://biit.cs.ut.ee/demi/).

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