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Distinct Modes of Mediator-Dependent Transcription at Heat Shock Protein Genes and Nuclear Stress Bodies

ABSTRACT: Cells adapt to environmental stress by reprogramming gene expression. During heat stress, the transcription factor HSF1 translocates into the nucleus and activates heat shockâ€“responsive genes, including the lncRNA HSATIII, thereby promoting formation of nuclear stress bodies (nSBs). We show that the Mediator subunit MED26 enhances HSATIII transcription and nSB formation through a mechanism distinct from its role at canonical heat shock protein (HSP) genes. Upon heat stress, MED26-containing Mediator is recruited to both HSP loci and nSBs through interactions with HSF1 and MED15. Notably, phosphorylation of the intrinsically disordered region (IDR) of HSF1 is particularly important for Mediator recruitment to nSBs. Acute loss of MED26 leads to dissociation of both Mediator and Pol II from HSP promoters, whereas at HSATIII loci Mediator is retained despite Pol II dissociation. These results indicate that MED26 acts as molecular switch that facilitates Mediator-Pol II holo-complex assembly at nSBs and promotes nSB formation during heat stress.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Hidehisa Takahashi

PROVIDER: PXD073807 | JPOST Repository | Fri Jul 17 00:00:00 BST 2026

REPOSITORIES: jPOST

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			Action	DRS
	20231127_LiMED26HSprogenesis.mgf	Mgf
	F006477.xml	Xml
	HeLa_NE.raw	Raw
	Li_MED26_HS_progenesis.xlsx	Xlsx
	MED26_HS_NE.raw	Raw

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Distinct Modes of Mediator-Dependent Transcription at Heat Shock Protein Genes and Nuclear Stress Bodies

Project description:Cells adapt to environmental stress by reprogramming gene expression. During heat stress, the transcription factor HSF1 translocates into the nucleus and activates heat shockâ€“responsive genes, including the lncRNA HSATIII, thereby promoting formation of nuclear stress bodies (nSBs). We show that the Mediator subunit MED26 enhances HSATIII transcription and nSB formation through a mechanism distinct from its role at canonical heat shock protein (HSP) genes. Upon heat stress, MED26-containing Mediator is recruited to both HSP loci and nSBs through interactions with HSF1 and MED15. Notably, phosphorylation of the intrinsically disordered region (IDR) of HSF1 is particularly important for Mediator recruitment to nSBs. Acute loss of MED26 leads to dissociation of both Mediator and Pol II from HSP promoters, whereas at HSATIII loci Mediator is retained despite Pol II dissociation. These results indicate that MED26 acts as molecular switch that facilitates Mediator-Pol II holo-complex assembly at nSBs and promotes nSB formation during heat stress.

2026-07-17 | PXD073817 | JPOST Repository

CPSF73 activation and 3’ Pol II pausing are lost during read-through transcription after heat shock [ChIP-seq]

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Project description:In nature, plants are often exposed to recurring adverse environmental conditions. Acclimation to high temperature stress entails transcriptional responses that are mediated by heat-shock transcription factors (HSFs), and they are primed to better withstand subsequent stress events. This heat stress (HS)-induced transcriptional memory results in more efficient re-induction of transcription upon recurring HS. However, the mechanisms by which HSFs recruit and enact the transcriptional machinery remain unclear. Here, we identified two subunits of the kinase module of the Mediator transcriptional co-regulator complex, CDK8 and MED12, as regulators of HS memory in Arabidopsis thaliana. Enhanced re-induction of gene expression after recurrent HS and physiological HS memory, as well as H3K4 methylation are compromised in cdk8 and med12 mutants. HSFA2 interacts with CDK8 during and after HS and recruits it to memory gene loci, where CDK8 binds in the promoter but also the gene body, together with core Mediator and RNA polymerase II (Pol II). Our data suggest that CDK8 resolves stalled Pol II complexes or promotes efficient recycling for subsequent cycles of transcription. As HSFA2, CDK8 is largely dispensable for the initial induction of gene expression after HS and thus promotes transcriptional memory independently of HS-dependent primary gene induction. Our findings provide a model for the complex role of the Mediator kinase module during transcriptional memory in multicellular eukaryotes through interaction with transcription factors, chromatin modifications and promotion of Pol II productivity.

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Mediator promotes CENP-A incorporation at fission yeast centromeres [ChIP-seq]

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Project description:O-GlcNAc is known to regulate the aggregation and condensate formation of several proteins, but how O-GlcNAc regulates protein solubilities globally has yet to be systematically investigated. Here, we employed a chemoproteomic workflow integrating selective enrichment and multiplex proteomics to quantify the solubilities of O-GlcNAcylated and non-modified proteins, as well as their role in RNA condensate formation. The solubilities were also quantified after heat stress and recovery to investigate the condensate formation during heat stress response. Surprisingly. we found O-GlcNAc leads to dramatic solubility decrease of the modified proteins, and the degree of solubility drop is related to the protein localization and functions. Site-specific analysis found the adjacent residues and secondary structures of the glycosites are pivotal for the effect of O-GlcNAc for solubility change, and the number of acidic residues is related to the different effect of O-GlcNAc in heat stress and recovery. Additionally, it was found that O-GlcNAc promotes the dissociation of RNA condensates during heat stress, while it enhances the formation of RNA condensates in the recovery phase. The glycosites that facilitate the dissociation or the formation of the RNA condensates are distinct, and the physiological properties of their surroundings residues are diverse. This work advances our understanding of the role of O-GlcNAc in regulating biomolecular condensates and will be a useful resource for future research in biomolecular condensates.

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