scholarly journals H3-K27M-Mutant Nucleosomes Interact with MLL1 to Shape the Glioma Epigenetic Landscape

2021 ◽  
Author(s):  
Noa Furth ◽  
Danielle Algranati ◽  
Bareket Dassa ◽  
Olga Beresh ◽  
Vadim Fedyuk ◽  
...  
Keyword(s):  
Single Molecule ◽  
Histone H3 ◽  
Epigenetic Landscape ◽  
Intrinsic Properties ◽  
Active Chromatin ◽  
Polycomb Repressive Complex 2 ◽  
Genome Wide ◽  
Genes Encoding ◽  
Poorly Differentiated ◽  
Epigenetic Patterns

Cancer-associated mutations in genes encoding histones dramatically reshape chromatin and support tumorigenesis. Lysine to methionine substitution of residue 27 on histone H3 (K27M) is a driver mutation in high-grade pediatric gliomas, known to abrogate Polycomb Repressive Complex 2 (PRC2) activity. We applied single-molecule systems to image individual nucleosomes and delineate the combinatorial epigenetic patterns associated with H3-K27M expression. We found that chromatin marks on H3-K27M-mutant nucleosomes are dictated both by their incorporation preferences and by intrinsic properties of the mutation. Mutant nucleosomes not only preferentially bind PRC2, but also directly interact with MLL1, thus leading to genome-wide redistribution of H3K4me3. H3-K27M-mediated deregulation of both repressive and active chromatin marks leads to unbalanced 'bivalent' chromatin, which may support a poorly differentiated cellular state. This study provides evidence for a direct effect of H3-K27M oncohistone on the MLL1-H3K4me3 pathway and highlights the capability of single-molecule tools to reveal mechanisms of chromatin deregulation in cancer.

scholarly journals KDM2B is a histone H3K79 demethylase and induces transcriptional repression via SIRT1-mediated chromatin silencing

2017 ◽  
Author(s):  
Joo-Young Kang ◽  
Ji-Young Kim ◽  
Kee-Beom Kim ◽  
Jin Woo Park ◽  
Hana Cho ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Histone H3 ◽  
Active Chromatin ◽  
Knockdown Cell ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Demethylase Activity ◽  
H4k16 Acetylation ◽  
H3k79 Methylation

AbstractThe methylation of histone H3 lysine 79 (H3K79) is an active chromatin marker and is prominant in actively transcribed regions of the genome. However, demethylase of H3K79 remains unknown despite intensive research. Here, we show that KDM2B (also known as FBXL10), a member of the Jumonji C family of proteins and known for its histone H3K36 demethylase activity, is a di- and tri-methyl H3K79 demethylase. We demonstrate that KDM2B induces transcriptional repression of HOXA7 and MEIS1 via occupancy of promoters and demethylation of H3K79. Furthermore, genome-wide analysis suggests that H3K79 methylation levels increase when KDM2B is depleted, indicating that KDM2B functions as an H3K79 demethylase in vivo. Finally, stable KDM2B-knockdown cell lines exhibit displacement of NAD+-dependent deacetylase SIRT1 from chromatin, with concomitant increases in H3K79 methylation and H4K16 acetylation. Our findings identify KDM2B as an H3K79 demethylase and link its function to transcriptional repression via SIRT1-mediated chromatin silencing.

Genome‐Wide DNA (hydroxy)methylation reveals the individual epigenetic landscape importance on osteogenic phenotype acquisition in periodontal ligament cells

2021 ◽  
Author(s):  
Rogério S. Ferreira ◽  
Rahyza I. F. Assis ◽  
Geórgia da S. Feltran ◽  
Iasmin Caroline do Rosário Palma ◽  
Beatriz G. Françoso ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Periodontal Ligament Cells ◽  
Epigenetic Landscape ◽  
Genome Wide ◽  
The Individual

scholarly journals Fast and efficient Rmap assembly using the Bi-labelled de Bruijn graph

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Kingshuk Mukherjee ◽  
Massimiliano Rossi ◽  
Leena Salmela ◽  
Christina Boucher
Keyword(s):  
Single Molecule ◽  
De Bruijn Graph ◽  
Anabas Testudineus ◽  
E Coli ◽  
Genome Wide ◽  
A Genome ◽  
De Bruijn ◽  
Optical Maps ◽  
Definition Of ◽  
Numeric Representation

AbstractGenome wide optical maps are high resolution restriction maps that give a unique numeric representation to a genome. They are produced by assembling hundreds of thousands of single molecule optical maps, which are called Rmaps. Unfortunately, there are very few choices for assembling Rmap data. There exists only one publicly-available non-proprietary method for assembly and one proprietary software that is available via an executable. Furthermore, the publicly-available method, by Valouev et al. (Proc Natl Acad Sci USA 103(43):15770–15775, 2006), follows the overlap-layout-consensus (OLC) paradigm, and therefore, is unable to scale for relatively large genomes. The algorithm behind the proprietary method, Bionano Genomics’ Solve, is largely unknown. In this paper, we extend the definition of bi-labels in the paired de Bruijn graph to the context of optical mapping data, and present the first de Bruijn graph based method for Rmap assembly. We implement our approach, which we refer to as rmapper, and compare its performance against the assembler of Valouev et al. (Proc Natl Acad Sci USA 103(43):15770–15775, 2006) and Solve by Bionano Genomics on data from three genomes: E. coli, human, and climbing perch fish (Anabas Testudineus). Our method was able to successfully run on all three genomes. The method of Valouev et al. (Proc Natl Acad Sci USA 103(43):15770–15775, 2006) only successfully ran on E. coli. Moreover, on the human genome rmapper was at least 130 times faster than Bionano Solve, used five times less memory and produced the highest genome fraction with zero mis-assemblies. Our software, rmapper is written in C++ and is publicly available under GNU General Public License at https://github.com/kingufl/Rmapper.

scholarly journals An Alternative Approach to ChIP-Seq Normalization Enables Detection of Genome-Wide Changes in Histone H3 Lysine 27 Trimethylation upon EZH2 Inhibition

PLoS ONE ◽  
2016 ◽  
Vol 11 (11) ◽  
pp. e0166438 ◽  
Author(s):  
Brian Egan ◽  
Chih-Chi Yuan ◽  
Madeleine Lisa Craske ◽  
Paul Labhart ◽  
Gulfem D. Guler ◽  
...  
Keyword(s):  
Histone H3 ◽  
Genome Wide ◽  
Alternative Approach

scholarly journals Elucidating the regulatory mechanism of Swi1 prion in global transcription and stress responses

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhiqiang Du ◽  
Jeniece Regan ◽  
Elizabeth Bartom ◽  
Wei-Sheng Wu ◽  
Li Zhang ◽  
...  
Keyword(s):  
Stress Responses ◽  
Regulation Of Transcription ◽  
Interacting Proteins ◽  
Environmental Stress Response ◽  
Key Factors ◽  
Cellular Functions ◽  
Beneficial Effects ◽  
Genome Wide ◽  
Genes Encoding ◽  
A Subunit

AbstractTranscriptional regulators are prevalent among identified prions in Saccharomyces cerevisiae, however, it is unclear how prions affect genome-wide transcription. We show here that the prion ([SWI+]) and mutant (swi1∆) forms of Swi1, a subunit of the SWI/SNF chromatin-remodeling complex, confer dramatically distinct transcriptomic profiles. In [SWI+] cells, genes encoding for 34 transcription factors (TFs) and 24 Swi1-interacting proteins can undergo transcriptional modifications. Several TFs show enhanced aggregation in [SWI+] cells. Further analyses suggest that such alterations are key factors in specifying the transcriptomic signatures of [SWI+] cells. Interestingly, swi1∆ and [SWI+] impose distinct and oftentimes opposite effects on cellular functions. Translation-associated activities, in particular, are significantly reduced in swi1∆ cells. Although both swi1∆ and [SWI+] cells are similarly sensitive to thermal, osmotic and drought stresses, harmful, neutral or beneficial effects were observed for a panel of tested chemical stressors. Further analyses suggest that the environmental stress response (ESR) is mechanistically different between swi1∆ and [SWI+] cells—stress-inducible ESR (iESR) are repressed by [SWI+] but unchanged by swi1∆ while stress-repressible ESR (rESR) are induced by [SWI+] but repressed by swi1∆. Our work thus demonstrates primarily gain-of-function outcomes through transcriptomic modifications by [SWI+] and highlights a prion-mediated regulation of transcription and phenotypes in yeast.

scholarly journals Enhanced sustainable green revolution yield via nitrogen-responsive chromatin modulation in rice

Science ◽  
2020 ◽  
Vol 367 (6478) ◽  
pp. eaaz2046 ◽  
Author(s):  
Kun Wu ◽  
Shuansuo Wang ◽  
Wenzhen Song ◽  
Jianqing Zhang ◽  
Yun Wang ◽  
...  
Keyword(s):  
Nitrogen Use Efficiency ◽  
Green Revolution ◽  
Agricultural Sustainability ◽  
Nitrogen Use ◽  
Polycomb Repressive Complex 2 ◽  
Della Proteins ◽  
Genome Wide ◽  
Use Efficiency ◽  
Low Nitrogen ◽  
Cereal Yields

Because environmentally degrading inorganic fertilizer use underlies current worldwide cereal yields, future agricultural sustainability demands enhanced nitrogen use efficiency. We found that genome-wide promotion of histone H3 lysine 27 trimethylation (H3K27me3) enables nitrogen-induced stimulation of rice tillering: APETALA2-domain transcription factor NGR5 (NITROGEN-MEDIATED TILLER GROWTH RESPONSE 5) facilitates nitrogen-dependent recruitment of polycomb repressive complex 2 to repress branching-inhibitory genes via H3K27me3 modification. NGR5 is a target of gibberellin receptor GIBBERELLIN INSENSITIVE DWARF1 (GID1)–promoted proteasomal destruction. DELLA proteins (characterized by the presence of a conserved aspartate-glutamate-leucine-leucine-alanine motif) competitively inhibit the GID1-NGR5 interaction and explain increased tillering of green revolution varieties. Increased NGR5 activity consequently uncouples tillering from nitrogen regulation, boosting rice yield at low nitrogen fertilization levels. NGR5 thus enables enhanced nitrogen use efficiency for improved future agricultural sustainability and food security.

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