The dynamic three-dimensional organization of the diploid yeast genome DOI Creative Commons
Seungsoo Kim, Ivan Liachko,

Donna Garvey Brickner

и другие.

eLife, Год журнала: 2017, Номер 6

Опубликована: Май 24, 2017

The budding yeast Saccharomyces cerevisiae is a long-standing model for the three-dimensional organization of eukaryotic genomes. However, even in this well-studied model, it unclear how homolog pairing diploids or environmental conditions influence overall genome organization. Here, we performed high-throughput chromosome conformation capture on diverged hybrid to obtain first global view diploid yeasts. After controlling Rabl-like orientation using polymer observe significant proximity that increases saturated culture conditions. Surprisingly, localized increase homologous interactions between HAS1-TDA1 alleles specifically under galactose induction and growth. This accompanied by relocalization nuclear periphery requires Nup2, suggesting role pore complexes. Together, these results reveal has dynamic complex 3D

Язык: Английский

Epigenetic and chromatin-based mechanisms in environmental stress adaptation and stress memory in plants DOI Creative Commons
Jörn Lämke, Isabel Bäurle

Genome biology, Год журнала: 2017, Номер 18(1)

Опубликована: Июнь 27, 2017

Plants frequently have to weather both biotic and abiotic stressors, evolved sophisticated adaptation defense mechanisms. In recent years, chromatin modifications, nucleosome positioning, DNA methylation been recognized as important components in these adaptations. Given their potential epigenetic nature, such modifications may provide a mechanistic basis for stress memory, enabling plants respond more efficiently recurring or even prepare offspring future assaults. this review, we discuss the involvement of responses current evidence on somatic, intergenerational, transgenerational memory.

Язык: Английский

Процитировано

646

Transcription regulation by the Mediator complex DOI
Julie Soutourina

Nature Reviews Molecular Cell Biology, Год журнала: 2017, Номер 19(4), С. 262 - 274

Опубликована: Дек. 6, 2017

Язык: Английский

Процитировано

514

The Mediator complex as a master regulator of transcription by RNA polymerase II DOI Open Access
William F. Richter, Shraddha Nayak, Janet Iwasa

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2022, Номер 23(11), С. 732 - 749

Опубликована: Июнь 20, 2022

Язык: Английский

Процитировано

202

Pioneer factors as master regulators of the epigenome and cell fate DOI
Aurélio Balsalobre, Jacques Drouin

Nature Reviews Molecular Cell Biology, Год журнала: 2022, Номер 23(7), С. 449 - 464

Опубликована: Март 9, 2022

Язык: Английский

Процитировано

182

The Mediator Complex: At the Nexus of RNA Polymerase II Transcription DOI
Celia Jerónimo, François Robert

Trends in Cell Biology, Год журнала: 2017, Номер 27(10), С. 765 - 783

Опубликована: Авг. 1, 2017

Язык: Английский

Процитировано

180

Glucocorticoid exposure during hippocampal neurogenesis primes future stress response by inducing changes in DNA methylation DOI Open Access
Nadine Provençal, Janine Arloth, Annamaria Cattaneo

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2019, Номер 117(38), С. 23280 - 23285

Опубликована: Авг. 9, 2019

Significance Prenatal stress exposure is associated with a wide range of health problems later in life. This may be mediated part via glucocorticoid (GC) during fetal development known to impact neurogenesis and induce epigenetic changes. Using human hippocampal progenitor cell line assess the effects GCs, we observe that GCs early results lasting changes DNA methylation (DNAm). Lasting DNAm alterations are significantly enhanced transcriptional response subsequent GC exposure. Our data suggest set point future responses by inducing Such altered points relate differential vulnerability

Язык: Английский

Процитировано

176

Histone H3 lysine K4 methylation and its role in learning and memory DOI Creative Commons
Bridget E. Collins, Celeste B. Greer,

Benjamin C. Coleman

и другие.

Epigenetics & Chromatin, Год журнала: 2019, Номер 12(1)

Опубликована: Янв. 7, 2019

Epigenetic modifications such as histone methylation permit change in chromatin structure without accompanying the underlying genomic sequence. A number of studies animal models have shown that dysregulation various components epigenetic machinery causes cognitive deficits at behavioral level, suggesting proper control is necessary for fundamental processes learning and memory. Histone H3 lysine K4 (H3K4) comprises one component control, global levels this mark are increased hippocampus during memory formation. Modifiers H3K4 needed formation, through studies, many same modifiers mutated human diseases. Indeed, all known methyltransferases four six demethylases been associated with impaired cognition a neurologic or psychiatric disorder. Cognitive impairment patients often manifests intellectual disability, consistent role As modification quintessentially, but not exclusively, transcriptional activity, provides unique insights into regulatory complexity writing, reading, erasing marks within an activated neuron. The following review will discuss connect it to events required developed nervous system. This include initial discussion most recent advances developing methodology analyze methylation, namely mass spectrometry deep sequencing, well how these methods can be applied more deeply understand biology brain. We then introduce core enzymatic mediating addition removal resulting signatures throughout neuronal genome. next foray brain, discussing changes formation retrieval, correlates methyltransferase deficiency region. Finally, we diseases connected each modulator summarize drugs target them.

Язык: Английский

Процитировано

155

Epigenetic regulation of abiotic stress memory: maintaining the good things while they last DOI Creative Commons
Vicky Oberkofler, Loris Pratx, Isabel Bäurle

и другие.

Current Opinion in Plant Biology, Год журнала: 2021, Номер 61, С. 102007 - 102007

Опубликована: Фев. 9, 2021

As sessile organisms, plants have evolved sophisticated ways to constantly gauge and adapt changing environmental conditions including extremes that may be harmful their growth development are thus perceived as stress. In nature, stressful events often chronic or recurring an initial stress prime a plant respond more efficiently subsequent event. An epigenetic basis of such memory was long postulated in recent years it has been shown this is indeed the case. High temperature proven excellent system unpick molecular somatic memory, which includes histone modifications nucleosome occupancy. This review discusses findings pinpoints open questions field.

Язык: Английский

Процитировано

133

Epigenetic regulation of thermomorphogenesis and heat stress tolerance DOI Open Access
Giorgio Perrella, Isabel Bäurle, Martijn van Zanten

и другие.

New Phytologist, Год журнала: 2022, Номер 234(4), С. 1144 - 1160

Опубликована: Янв. 17, 2022

Summary Many environmental conditions fluctuate and organisms need to respond effectively. This is especially true for temperature cues that can change in minutes seasons often follow a diurnal rhythm. Plants cannot migrate most regulate their temperature. Therefore, broad array of responses have evolved deal with from freezing heat stress. A particular response mildly elevated temperatures called thermomorphogenesis, suite morphological adaptations includes thermonasty, formation thin leaves elongation growth petioles hypocotyl. Thermomorphogenesis allows optimal performance suboptimal by enhancing the cooling capacity. When rise further, stress tolerance mechanisms be induced enable plant survive stressful temperature, which typically comprises cellular protection memory thereof. Induction depend on gene expression regulation, governed diverse epigenetic processes. In this Tansley review we update current knowledge regulation signalling response, focus thermomorphogenesis memory. highlight emerging role H3K4 methylation marks pathways.

Язык: Английский

Процитировано

95

The Mediator kinase module: an interface between cell signaling and transcription DOI Creative Commons
Olivia Luyties, Dylan J. Taatjes

Trends in Biochemical Sciences, Год журнала: 2022, Номер 47(4), С. 314 - 327

Опубликована: Фев. 19, 2022

The Mediator kinase module transforms function through physical interaction and its activity.The regulates transcription by altering factor at enhancers promoters.Rapid, stimulus-specific transcriptional responses are enabled the module.By controlling (TF) polymerase II (pol II) activity, helps convert signaling inputs to outputs. complex controls RNA activity coordinating assembly of pol regulatory factors start sites mediating interactions between enhancer-bound (TFs) enzyme. structure is completely altered upon binding module, a multi-subunit that contains CDK8 or vertebrate-specific paralog CDK19. Here, we review mechanisms which transcription, emphasizing impact on TF elongation, enhancer function, chromatin architecture. We also highlight how integrates pathways with enable rapid, responses, as well links human disease. (see Glossary) genome-wide regulator transcription; consequently, itself targeted an array regulate function. For example, sequence-specific, DNA-binding TFs bind control recruitment specific genomic loci. Also, reversibly associates (forming what here call CDK-Mediator) in several ways. Conserved from yeast humans, consists four subunits: kinase, CCNC, MED12, MED13. However, vertebrates evolved subunit paralogs, called CDK19, MED12L, MED13L (Box 1), expand functional diversity ways remain poorly defined. Not surprisingly, subunits required for mammalian embryogenesis [1.Li N. et al.Cyclin C haploinsufficient tumour suppressor.Nat. Cell Biol. 2014; 16: 1080-1091Google Scholar, 2.Miao Y.L. al.Mediator component MED13 zygotic genome activation postimplantation development mouse.Biol. Reprod. 2018; 98: 449-464Google 3.Westerling T. al.Cdk8 essential preimplantation mouse development.Mol. Cell. 2007; 27: 6177-6182Google 4.Rocha P.P. al.Med12 early canonical Wnt Wnt/PCP signaling.Development. 2010; 137: 2723-2731Google Scholar] linked myriad diseases 2).Box 1Vertebrate-specific paralogs subunitsThe conserved among eukaryotes, but CDK8, emerged (Figure I). Each expressed different chromosomes appears be mutually exclusive within [52.Galbraith M.D. al.HIF1A employs CDK8-Mediator stimulate RNAPII elongation response hypoxia.Cell. 2013; 153: 1327-13239Google Scholar]. Comparatively little known about these connections disease have been discovered (Table S1 supplemental information online).CDK8 CDK19 highest sequence identity inhibitors invariably block both proteins. show evidence redundant [109.Sooraj D. al.MED12 BRD4 cooperate sustain cancer growth loss mediator kinase.Mol. 2022; 82: 123-139Google nonredundant functions each has shown kinase-dependent -independent [25.Steinparzer I. al.Transcriptional IFN-gamma require pause release mechanistically distinct functions.Mol. 2019; 76: 485-499Google Scholar,87.Audetat K.A. al.A kinase-independent role cyclin-dependent 19 p53 response.Mol. 2017; 37e00626-16Google Scholar,109.Sooraj Scholar,117.Menzl BCR-ABL1(+) leukemia.Nat. Commun. 10: 4741Google Scholar].The MED12 protein implicated numerous X-linked online) X chromosome, whereas MED12L gene resides chromosome 3. Interestingly, Xist repression (CDK19 no effect) mice [118.Postlmayr A. establishment H3K27me3 development.Development. 2020; 147dev175141Google shows more restricted expression across tissues compared MED12. Whereas necessary [8.Park M.J. al.Oncogenic exon 2 mutations disrupt allosteric cyclin C-CDK8/19.J. Chem. 293: 4870-4882Google Scholar,81.Knuesel M.T. al.The subcomplex histone requires Med12 can independently Mediator.Mol. 2009; 29: 650-661Google Scholar], it unknown whether activates CDK8/19 similarity N-terminal helix I) suggests similar activation.One basic link [10.Knuesel molecular switch co-activator function.Genes Dev. 23: 439-451Google Scholar,11.Tsai K.L. Mediator-CDK8 association Mediator-RNA interaction.Nat. Struct. Mol. 20: 611-619Google Notably, proteomics data suggest modules containing (instead MED13) maintain [39.Ebmeier C.C. Taatjes D.J. Activator-Mediator Mediator-cofactor interactions.Proc. Natl. Acad. Sci. U. S. 107: 11283-11288Google Scholar,119.Sato set consensus identified multidimensional identification technology.Mol. 2004; 14: 685-691Google Moreover, ubiquitylated FBW7, initiates dissociation degradation [110.Davis M.A. SCF-Fbw7 ubiquitin ligase degrades Mediator.Genes 151-156Google Clinical similar, not identical, biological roles online).Box 2Mediator diseaseMutations cause disability online), broadly grouped into two categories: neurological/developmental disorders (reviewed [7.Srivastava Kulshreshtha R. Insights clinical relevance subunit, diseases.J. Physiol. 2021; 236: 3163-3177Google Scholar]). In addition, wide range cancers subunits, summarized recent reviews [121.Dannappel M.V. al.Molecular vivo modules.Front. 6: 171Google Scholar,122.Roninson I.B. al.Identifying impacted CDK8/19.Cells. 8: 821Google Scholar].Three medically related intellectual/developmental syndromes MED12: Opitz-Kaveggia, Lujan, Ohdo syndrome. Furthermore, domains associated intellectual exhibit comparable phenotypes individuals online). introduction could compensate deletion Drosophila, mutant neurological not, resulting seizures reduced fitness surviving flies [123.Chung H.L. al.De novo variants syndrome involving epileptic encephalopathy.Am. J. Hum. Genet. 106: 717-725Google Likewise, induced pathogenic mutants resulted developmental defects [124.Tian al.Somatic de germline MEDs neural tube defects.Front. 9641831Google These results disease-associated CDK19.Mutations nonmalignant uterine leiomyoma most well-studied changes enhancer-promoter looping architecture [79.Moyo M.B. al.Altered landscape engagement underlie dysregulation leiomyomas.Nat. 11: 1019Google negatively Scholar,9.Turunen M. al.Uterine leiomyoma-linked mediator-associated CDK activity.Cell Rep. 7: 654-660Google Such consistent regulation super-enhancer [67.Kuuluvainen E. al.Depletion represses superenhancer-associated genes colon cells.Mol. 38e00573-17Google Scholar,74.Pelish H.E. inhibition further super-enhancer-associated AML.Nature. 2015; 526: 273-276Google Scholar,75.Lynch C.J. al.Global hyperactivation stabilizes naive pluripotency kinases.Nat. 22: 1223-1238Google Scholar].Targeting therapeutic benefit remains work progress, novel strategies continue emerge. Firestein lab showed bromodomain extraterminal domain (BET) (e.g., JQ1) may complement + certain compensatory increases occupancy BET were observed double knockout cells (HCT116 DLD1), suggesting cooperativity agreement other studies [51.Donner A.J. al.CDK8 positive serum network.Nat. 17: 194-201Google Scholar,125.Bhagwat A.S. al.BET releases select cis-regulatory elements.Cell 2016; 15: 519-530Google activation. One Mutations Three Targeting Although current structural only CDK8-CCNC dimer [5.Schneider E.V. CDK8/CycC implicates specificity CDK/cyclin family reveals deep pocket binder.J. 2011; 412: 251-266Google cryogenic electron microscopy (cryoEM) (Saccharomyces cerevisiae) was recently determined Tsai [6.Li Y.C. al.Structure noncanonical Cdk8 mechanism Argonaute-containing module.Sci. Adv. 7eabd4484Google This provided first high-resolution large Med13 subunits. key module. N terminus interacts Cdk8–Ccnc 1). mutated variety clustering around residues 36–44 Structural coworkers occupy complex. otherwise disordered loop, allows substrate access active site Additionally, prior Boyer oncogenic model Med12-dependent likely humans. While details available, Cramer completed crosslinking-mass spectrometry analysis (S. CDK-Mediator [12.Osman II.J. 296100734Google extensive Mediator, including and/or Med19 Med10, Med10 reside hook [13.Zhao H. Tail core.Nat. 12: 1355Google represents interface TFIIH-associated later). this review, some considering past context results. enables cell cascades help 'reprogram' patterns changing conditions. then discuss module-dependent stages (initiation, pausing, elongation) new clarified expanded biochemical cell-based experiments. Finally, represent powerful elements coordinate type- programs outline contribute looping. Throughout, areas understanding limited conclude open questions future research. genome-wide, remodelers, way, serve 'master regulators' pre-initiation (PIC) Activation causes phosphorylation nuclear localization 2). As examples: (i) interferon-induced STAT triggers their allow target activation, (ii) ELK1 phosphorylated during MAPK pathway enhances ELK1-dependent [14.Balamotis al.Complexity domain-Mediator interface.Sci. Signal. 2: ra20Google representative examples, endpoints cascades. Importantly, common targets kinases later), yielding direct signaling. Coordination evident ancient metabolism. Signaling metabolic integrated interdependent, such will trigger adaptation, vice versa 2) [15.Zhu Thompson C.B. Metabolic proliferation.Nat. Rev. 436-450Google flux directly enzymes phosphorylation), they modulate well. organisms cerevisiae, coordinates nutrients [16.Khakhina al.Med13p prevents mitochondrial fission programmed death retention C.Mol. 25: 2807-2816Google 17.Lindsay A.K. al.Analysis Candida albicans defective reveal metabolism biofilm formation.PLoS 10e1004567Google 18.Mousley sterol-binding endosomal lipid TOR nitrogen sensing.Cell. 2012; 148: 702-715Google via [19.Hirst al.GAL4 regulated holoenzyme-associated SRB10/CDK8.Mol. 1999; 3: 673-678Google Scholar,20.Nelson C. al.Srb10/Cdk8 filamentous phosphorylating Ste12.Nature. 2003; 421: 187-190Google Similarly, indirectly metazoans modification TFs. cells, phosphorylates major regulators metabolism, SREBP [21.Zhao X. al.Regulation lipogenesis 8-mediated SREBP-1.J. Clin. Invest. 122: 2417-2427Google Notch ICD Scholar,22.Fryer al.Mastermind recruits CycC:Cdk8 phosphorylate notch turnover.Mol. 509-520Google SMAD1/3 [23.Alarcon al.Nuclear CDKs drive Smad turnover BMP TGF-b pathways.Cell. 139: 757-769Google STAT1/3/5a [24.Bancerek STAT1 selectively interferon response.Immunity. 38: 250-262Google insulin, WNT/β-catenin, TGFβ, cascades, respectively. CDK8-dependent stability co

Язык: Английский

Процитировано

80