Chromatin SUMOylation in heat stress: To protect, pause and organise?

Niskanen, Einari A.; Palvimo, Jorma J.

doi:10.1002/bies.201600263

Cited by 37 publications

(53 citation statements)

References 92 publications

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“…43 ). This post-translational modification is thought to act like 'glue' 44,45 , probably increasing the residence time of N-TEFs at chromatin to enable SITA. In this context, how different N-TEFs cooperate with each other, either in a gene-dependent manner or globally, and how such interactions operate during recovery from stress will be critical to understand.…”

Section: Discussionmentioning

confidence: 99%

Nascent-protein ubiquitination is required for heat shock–induced gene downregulation in human cells

Aprile-Garcia

Tomar

Hummel

et al. 2019

Nat Struct Mol Biol

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hen eukaryotic cells are exposed to environmental stress, they mount an adaptive, conserved and coordinated response at the levels of transcription, translation, cell cycle and metabolism. The transcriptional response called the heat-shock response is typified by upregulation of heat-shock proteins or chaperones driven by the transcription factor heatshock factor (HSF) 1. Initially identified using heat-shock stress, the conserved HSF-driven response is now known to be induced by a variety of cellular conditions 2. Clinical studies have highlighted the relevance of the heat-shock response in cancer and neurodegeneration 3,4. Early studies have shown that stress such as heat shock not only upregulates chaperone genes, but also causes transcriptional downregulation of a handful of genes tested 5,6. Recent genome-wide technologies have confirmed a critical aspect of the heat-shock response: transcriptional downregulation of many highly expressed genes involved in metabolism, protein synthesis and cell cycle 7,8. Stress-induced transcriptional attenuation (SITA) is a rapid process conserved across Drosophila melanogaster 9 , mouse 7 and human cells 10. By downregulating the transcription of key genes, cells probably shift their resources from growth-promoting anabolic activities to dealing with proteotoxic stress. Despite the importance and conserved nature of SITA, relatively little is known about its underlying mechanistic basis. Two key questions need to be addressed: first, how are the rapid and reversible changes in transcription achieved at a molecular level; and second, how is the stress of heat shock sensed and communicated to transcriptional effectors? The primary stress sensor for chaperone upregulation, HSF, is not required for SITA 7 , suggesting an HSF-independent mechanism of stress sensing. How this mechanism is integrated with cellular stress response pathways is not understood. Metazoan transcription proceeds through two highly regulated steps 11,12. First, recruitment of RNA polymerase II (RNA Pol II) to core promoters leads to formation of a pre-initiation complex that transcribes about 20-60 bases downstream of transcription start sites (TSSs) and pauses. Sequence-specific transcription factors along with general transcription factors orchestrate this step. Second, release of promoter-proximal-paused RNA Pol II into productive elongation enables generation of a full-length transcript. Interplay between positive and negative transcription elongation factors (P-TEFs and N-TEFs, respectively) determines the fate of paused RNA Pol II, which is either termination followed by dissociation from promoters or transition to its elongating form. N-TEFs comprise several complexes including negative elongation factor (NELF), DRB-sensitivity inducing factor (DSIF), Integrator, tripartite motif containing 28 (TRIM28) and polymerase-associated factor 1 (PAF1) 13-16. N-TEFs oppose the elongation activity of P-TEFb, which consists of cyclin-dependent kinase 9 (Cdk9) and cyclin T 17. How stress affects the activity ...

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Section: Discussionmentioning

confidence: 99%

Nascent-protein ubiquitination is required for heat shock–induced gene downregulation in human cells

Aprile-Garcia

Tomar

Hummel

et al. 2019

Nat Struct Mol Biol

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“…Besides parylation, conjugation of Small Ubiquitin-like MOdifier (SUMO) to chromatin-bound proteins has been suggested to contribute to formation of chromatin domains and insulate regions during stress (reviewed in 98,105 ). Sumoylation of the proteome is, indeed, a hallmark of heat, osmotic, ethanol, metabolic and genotoxic stresses 105–109 , and a large-scale, selective chromatin sumoylation occurs upon heat shock, particularly at active genes and Pol II pause sites 27 .…”

Section: Chromatin Remodelling Upon Stressmentioning

confidence: 99%

“…Indeed, one of the mechanisms of enhancer-mediated transcriptional control involves increasing the local concentration of the transcription machinery, which could be coordinated by compartments that retain, or restrict, the access of transcriptional regulators 112 . The dynamic formation of chromatin domains likely involves protein networks including architectural proteins 90 , transcription machinery and factor binding 113 , as well as chemical moieties at the chromatin 98,105 .…”

Section: Chromatin Remodelling Upon Stressmentioning

confidence: 99%

Molecular mechanisms driving transcriptional stress responses

Vihervaara¹,

Duarte²,

Lis³

2018

Nat Rev Genet

216

224

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Proteotoxic stress, that is, stress caused by protein misfolding and aggregation, triggers the rapid and global reprogramming of transcription at genes and enhancers. Genome-wide assays that track transcriptionally-engaged RNA polymerase II (Pol II) at nucleotide resolution have provided key insights into the underlying molecular mechanisms that regulate transcriptional responses to stress. In addition, recent kinetic analyses on transcriptional control under heat stress have shown how cells ‘prewire’ and rapidly execute genome-wide changes in transcription while concurrently becoming poised for recovery. The regulation of Pol II at genes and enhancers in response to heat stress is coupled to chromatin modification and compartmentalization, as well as to co-transcriptional RNA processing. These mechanistic features seem to apply broadly to other coordinated genome-regulatory responses.

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“…Although SUMOylation has occasionally been linked to gene activation (Niskanen and Palvimo, 2017), the modification of transcription factors or transcriptional co-regulators restrains gene activation in most cases (Wotton et al, 2017). A recurrent theme is that chromatin-associated SUMOylation facilitates the establishment of a repressive environment, whereas deSUMOylation by SENPs counters this process, thereby contributing to gene activation (Niskanen and Palvimo, 2017;Wotton et al, 2017). At the center of these activities are chromatin-modifying enzyme complexes that act as epigenetic regulators (see poster).…”

Section: Senps In Chromatin Remodeling and The Control Of Gene Expresmentioning

confidence: 99%

SUMO-specific proteases and isopeptidases of the SENP family at a glance

Kunz

Piller

Müller

2018

Journal of Cell Science

208

151

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The ubiquitin-related SUMO system controls many cellular signaling networks. In mammalian cells, three SUMO forms (SUMO1, SUMO2 and SUMO3) act as covalent modifiers of up to thousands of cellular proteins. SUMO conjugation affects cell function mainly by regulating the plasticity of protein networks. Importantly, the modification is reversible and highly dynamic. Cysteine proteases of the sentrin-specific protease (SENP) family reverse SUMO conjugation in mammalian cells. In this Cell Science at a Glance article and the accompanying poster, we will summarize how the six members of the mammalian SENP family orchestrate multifaceted deconjugation events to coordinate cell processes, such as gene expression, the DNA damage response and inflammation.

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Chromatin SUMOylation in heat stress: To protect, pause and organise?

Cited by 37 publications

References 92 publications

Nascent-protein ubiquitination is required for heat shock–induced gene downregulation in human cells

Nascent-protein ubiquitination is required for heat shock–induced gene downregulation in human cells

Molecular mechanisms driving transcriptional stress responses

SUMO-specific proteases and isopeptidases of the SENP family at a glance

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