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

Donna Garvey Brickner

et al.

eLife, Journal Year: 2017, Volume and Issue: 6

Published: May 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

Language: Английский

Epigenetic transcriptional memory DOI

Agustina D’Urso,

Jason H. Brickner

Current Genetics, Journal Year: 2016, Volume and Issue: 63(3), P. 435 - 439

Published: Nov. 2, 2016

Language: Английский

Citations

134
Metazoan Nuclear Pores Provide a Scaffold for Poised Genes and Mediate Induced Enhancer-Promoter Contacts DOI Creative Commons
Pau Pascual‐García,

Brian Debo,

Jennifer R. Aleman

et al.

Molecular Cell, Journal Year: 2017, Volume and Issue: 66(1), P. 63 - 76.e6

Published: March 30, 2017

Language: Английский

Citations

130
Nuclear pore complexes and regulation of gene expression DOI

Marcela Raı́ces,

Maximiliano A. D’Angelo

Current Opinion in Cell Biology, Journal Year: 2017, Volume and Issue: 46, P. 26 - 32

Published: Jan. 11, 2017

Language: Английский

Citations

117
Regulatory functions of the Mediator kinases CDK8 and CDK19 DOI Creative Commons

Charli B. Fant,

Dylan J. Taatjes

Transcription, Journal Year: 2018, Volume and Issue: 10(2), P. 76 - 90

Published: Dec. 26, 2018

The Mediator-associated kinases CDK8 and CDK19 function in the context of three additional proteins: CCNC MED12, which activate CDK8/CDK19 kinase function, MED13, enables their association with Mediator complex. affect RNA polymerase II (pol II) transcription indirectly, through phosphorylation factors by controlling structure function. In this review, we discuss cellular roles mechanisms that enable biological functions. We focus on sequence-specific, DNA-binding other substrates, how or may metabolic transcriptional reprogramming enhancers chromatin looping. also summarize inhibitors therapeutic potential. Throughout, note conserved divergent functions between yeast mammalian CDK8, highlight many aspects module remain enigmatic, ranging from potential pol promoter-proximal pausing to liquid-liquid phase separation.

Language: Английский

Citations

105
Chromatin regulation of somatic abiotic stress memory DOI Creative Commons
Isabel Bäurle, Inês Trindade

Journal of Experimental Botany, Journal Year: 2020, Volume and Issue: 71(17), P. 5269 - 5279

Published: Feb. 19, 2020

Abstract In nature, plants are often subjected to periods of recurrent environmental stress that can strongly affect their development and productivity. To cope with these conditions, remember a previous stress, which allows them respond more efficiently subsequent phenomenon known as priming. This ability be maintained at the somatic level for few days or weeks after is perceived, suggesting store information past during this recovery phase. While immediate responses single event have been extensively studied, knowledge on priming effects how memory stored still scarce. At molecular level, condition involves changes in chromatin structure organization, may independently from transcription. review, we will summarize most recent developments field discuss different levels regulation contribute plant abiotic memory.

Language: Английский

Citations

82
Rebelled epigenome: histone H3S10 phosphorylation and H3S10 kinases in cancer biology and therapy DOI Creative Commons
Dorota Komar, Przemysław Juszczyński

Clinical Epigenetics, Journal Year: 2020, Volume and Issue: 12(1)

Published: Oct. 14, 2020

Abstract Background With the discovery that more than half of human cancers harbor mutations in chromatin proteins, deregulation epigenetic mechanisms has been recognized a hallmark malignant transformation. Post-translational modifications (PTMs) histone as main components regulatory machinery, are also broadly accepted therapeutic target. Current “epigenetic” therapies target predominantly writers, erasers and readers acetylation (to lesser extent) methylation, leaving other types PTMs largely unexplored. One them is phosphorylation serine 10 on H3 (H3S10ph). Main body H3S10ph emerging an important player initiation propagation cancer, it facilitates cellular transformation participates fundamental functions. In normal cells this mark dictates hierarchy additional involved formation protein binding scaffolds, transcriptional regulation, blocking repressive information shielding gene regions from heterochromatin spreading. During cell division, essential for chromosome condensation segregation. It function specific DNA–RNA hybrids, called R-loops, which modulate transcription facilitate chromosomal instability. Increase observed numerous cancer its abundance associated with inferior prognosis. Many H3S10-kinases, including MSK1/2, PIM1, CDK8 AURORA kinases, have long considered targets therapy. However, since these proteins participate critical processes, signal transduction, apoptotic signaling, metabolic fitness transcription, their functions often neglected. Conclusions enzymes responsible deposition modification activity oncogenesis. Epigenetic-drugs targeting axis modifications, potentially combination conventional or targeted therapy, provide promising angle search knowledge-driven strategies oncology.

Language: Английский

Citations

82
SPT5 stabilization of promoter-proximal RNA polymerase II DOI Creative Commons
Yuki Aoi,

Yoh-hei Takahashi,

Avani P. Shah

et al.

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(21), P. 4413 - 4424.e5

Published: Sept. 3, 2021

Language: Английский

Citations

75
Functional mechanisms and abnormalities of the nuclear lamina DOI
Adam Karoutas, Asifa Akhtar

Nature Cell Biology, Journal Year: 2021, Volume and Issue: 23(2), P. 116 - 126

Published: Feb. 1, 2021

Language: Английский

Citations

73
Inducible epigenome editing probes for the role of histone H3K4 methylation in Arabidopsis heat stress memory DOI Creative Commons
Vicky Oberkofler, Isabel Bäurle

PLANT PHYSIOLOGY, Journal Year: 2022, Volume and Issue: 189(2), P. 703 - 714

Published: March 11, 2022

Abstract Histone modifications play a crucial role in the integration of environmental signals to mediate gene expression outcomes. However, genetic and pharmacological interference often causes pleiotropic effects, creating urgent need for methods that allow locus-specific manipulation histone modifications, preferably an inducible manner. Here, we report system epigenome editing Arabidopsis (Arabidopsis thaliana) using heat-inducible dCas9 target JUMONJI (JMJ) H3 lysine 4 (H3K4) demethylase domain locus interest. As model locus, ASCORBATE PEROXIDASE2 (APX2) shows transcriptional memory after heat stress (HS), correlating with H3K4 hyper-methylation. We show dCas9–JMJ is targeted HS-dependent manner APX2 HS-induced overaccumulation trimethylation (H3K4me3) decreases when binds locus. This results reduced HS-mediated at Targeting enzymatically inactive JMJ protein analogous affected less than active protein; however, still observed decrease methylation levels. Thus, targeting was effective reducing effect not fully dependent on enzyme activity eraser domain, fusion may act part independently its activity. underlines caution design interpretation studies. expect our versatile be especially useful studying temporal dynamics chromatin modifications.

Language: Английский

Citations

45
The Mediator kinase module enhances polymerase activity to regulate transcriptional memory after heat stress in Arabidopsis DOI Creative Commons
Tim Crawford,

Lara Siebler,

Aleksandra Sulkowska

et al.

The EMBO Journal, Journal Year: 2024, Volume and Issue: 43(3), P. 437 - 461

Published: Jan. 16, 2024

Abstract Plants are often exposed to recurring adverse environmental conditions in the wild. Acclimation high temperatures entails transcriptional responses, which prime plants better withstand subsequent stress events. Heat (HS)-induced memory results more efficient re-induction of transcription upon recurrence heat stress. Here, we identified CDK8 and MED12, two subunits kinase module co-regulator complex, Mediator, as promoters associated histone modifications Arabidopsis. is recruited heat-stress genes by HEAT SHOCK TRANSCRIPTION FACTOR A2 (HSFA2). Like HSFA2, largely dispensable for initial gene induction HS, its function thus independent primary activation. In addition promoter start region target genes, also binds their 3ʹ-region, where it may promote elongation, termination, or rapid re-initiation RNA polymerase II (Pol II) complexes during bursts. Our work presents a complex role Mediator multicellular eukaryotes, through interactions with factors, chromatin modifications, promotion Pol efficiency.

Language: Английский

Citations

10