scholarly journals Structural basis for COMPASS recognition of an H2B-ubiquitinated nucleosome

2019 ◽  
Author(s):  
Evan J. Worden ◽  
Xiangbin Zhang ◽  
Cynthia Wolberger
Keyword(s):  
Histone Methylation ◽  
Structural Basis ◽  
Structural Rearrangements ◽  
H3k4 Methylation ◽  
Core Complex ◽  
Histone H2b ◽  
Protein Core ◽  
The Face ◽  
Histone H3k4

ABSTRACTMethylation of histone H3K4 is a hallmark of actively transcribed genes that depends on mono-ubiquitination of histone H2B (H2B-Ub). H3K4 methylation in yeast is catalyzed by Set1, the methyltransferase subunit of COMPASS. We report here the cryo-EM structure of a six-protein core COMPASS subcomplex, which can methylate H3K4 and be stimulated by H2B-Ub, bound to a ubiquitinated nucleosome. Our structure shows that COMPASS spans the face of the nucleosome, recognizing ubiquitin on one face of the nucleosome and methylating H3 on the opposing face. As compared to the structure of the isolated core complex, Set1 undergoes multiple structural rearrangements to cement interactions with the nucleosome and with ubiquitin. The critical Set1 RxR motif adopts a helix that mediates bridging contacts between the nucleosome, ubiquitin and COMPASS. The structure provides a framework for understanding mechanisms of trans-histone cross-talk and the dynamic role of H2B ubiquitination in stimulating histone methylation.

scholarly journals Structural basis for COMPASS recognition of an H2B-ubiquitinated nucleosome

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Evan J Worden ◽  
Xiangbin Zhang ◽  
Cynthia Wolberger
Keyword(s):  
Histone Methylation ◽  
Structural Basis ◽  
Structural Rearrangements ◽  
H3k4 Methylation ◽  
Core Complex ◽  
Histone H2b ◽  
Protein Core ◽  
The Face ◽  
Histone H3k4

Methylation of histone H3K4 is a hallmark of actively transcribed genes that depends on mono-ubiquitination of histone H2B (H2B-Ub). H3K4 methylation in yeast is catalyzed by Set1, the methyltransferase subunit of COMPASS. We report here the cryo-EM structure of a six-protein core COMPASS subcomplex, which can methylate H3K4 and be stimulated by H2B-Ub, bound to a ubiquitinated nucleosome. Our structure shows that COMPASS spans the face of the nucleosome, recognizing ubiquitin on one face of the nucleosome and methylating H3 on the opposing face. As compared to the structure of the isolated core complex, Set1 undergoes multiple structural rearrangements to cement interactions with the nucleosome and with ubiquitin. The critical Set1 RxxxRR motif adopts a helix that mediates bridging contacts between the nucleosome, ubiquitin and COMPASS. The structure provides a framework for understanding mechanisms of trans-histone cross-talk and the dynamic role of H2B ubiquitination in stimulating histone methylation.

scholarly journals Targeting the scaffolding role of LSD1 (KDM1A) poises acute myeloid leukemia cells for retinoic acid–induced differentiation

2020 ◽  
Vol 6 (15) ◽  
pp. eaax2746 ◽  
Author(s):  
Roberto Ravasio ◽  
Elena Ceccacci ◽  
Luciano Nicosia ◽  
Amir Hosseini ◽  
Pier Luigi Rossi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Retinoic Acid ◽  
Myeloid Leukemia ◽  
H3k4 Methylation ◽  
Acute Myeloid Leukemia Cells ◽  
Histone H3k4 ◽  
Expression Program ◽  
Differentiation Gene ◽  
Acute Myeloid

The histone demethylase LSD1 is deregulated in several tumors, including leukemias, providing the rationale for the clinical use of LSD1 inhibitors. In acute promyelocytic leukemia (APL), pharmacological doses of retinoic acid (RA) induce differentiation of APL cells, triggering degradation of the PML-RAR oncogene. APL cells are resistant to LSD1 inhibition or knockout, but targeting LSD1 sensitizes them to physiological doses of RA without altering of PML-RAR levels, and extends survival of leukemic mice upon RA treatment. The combination of RA with LSD1 inhibition (or knockout) is also effective in other non-APL, acute myeloid leukemia (AML) cells. Nonenzymatic activities of LSD1 are essential to block differentiation, while RA with targeting of LSD1 releases a differentiation gene expression program, not strictly dependent on changes in histone H3K4 methylation. Integration of proteomic/epigenomic/mutational studies showed that LSD1 inhibitors alter the recruitment of LSD1-containing complexes to chromatin, inhibiting the interaction between LSD1 and the transcription factor GFI1.

scholarly journals FANCI plays an essential role in spermatogenesis and regulates meiotic histone methylation

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Lan Xu ◽  
Weiwei Xu ◽  
Duan Li ◽  
Xiaoxia Yu ◽  
Fei Gao ◽  
...  
Keyword(s):  
Histone Methylation ◽  
Molecular Basis ◽  
Essential Role ◽  
Seminiferous Tubules ◽  
Nonobstructive Azoospermia ◽  
Core Complex ◽  
Interstrand Cross Links ◽  
Cross Links ◽  
Underlying Mechanisms

AbstractFANCI is an essential component of Fanconi anemia pathway, which is responsible for the repair of DNA interstrand cross-links (ICLs). As an evolutionarily related partner of FANCD2, FANCI functions together with FANCD2 downstream of FA core complex. Currently, growing evidences showed that the essential role of FA pathway in male fertility. However, the underlying mechanisms for FANCI in regulating spermatogenesis remain unclear. In the present study, we found that the male Fanci−/− mice were sterile and exhibited abnormal spermatogenesis, including massive germ cell apoptosis in seminiferous tubules and dramatically decreased number of sperms in epididymis. Besides, FANCI deletion impaired maintenance of undifferentiated spermatogonia. Further investigation indicated that FANCI was essential for FANCD2 foci formation and regulated H3K4 and H3K9 methylation on meiotic sex chromosomes. These findings elucidate the role and mechanism of FANCI during spermatogenesis in mice and provide new insights into the etiology and molecular basis of nonobstructive azoospermia.

scholarly journals Distinct requirements for the COMPASS core subunits Set1, Swd1, and Swd3 during meiosis in the budding yeast Saccharomyces cerevisiae

2021 ◽  
Author(s):  
Brandon M Trainor ◽  
Kerri Ciccaglione ◽  
Miranda Czymek ◽  
Michael J Law
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Chromosome Segregation ◽  
Chromatin Conformation ◽  
H3k4 Methylation ◽  
Yeast Saccharomyces Cerevisiae ◽  
The Core ◽  
Methylation Mark ◽  
Histone H3k4 ◽  
Transcription Program

Abstract Meiosis-specific chromatin structures, guided by histone modifications, are critical mediators of a meiotic transient transcription program and progression through prophase I. Histone H3K4 can be methylated up to three times by the Set1-containing COMPASS complex and each methylation mark corresponds to a different chromatin conformation. The level of H3K4 modification is directed by the activity of additional COMPASS components. In this study, we characterized the role of the COMPASS subunits during meiosis in S. cerevisiae. In vegetative cells, previous studies revealed a role for subunits Swd2, Sdc1, and Bre2 for H3K4me2 while Spp1 supported trimethylation. However, we found that Bre2 and Sdc1 are required for H3K4me3 as yeast prepare to enter meiosis while Spp1 is not. Interestingly, we identified distinct meiotic functions for the core COMPASS complex members that required for all H3K4me, Set1, Swd1, and Swd3. While Set1 and Swd1 are required for progression through early meiosis, Swd3 is critical for late meiosis and spore morphogenesis. Furthermore, the meiotic requirement for Set1 is independent of H3K4 methylation, suggesting the presence of non-histone substrates. Finally, checkpoint suppression analyses indicate that Set1 and Swd1 are required for both homologous recombination and chromosome segregation. These data suggest that COMPASS has important new roles for meiosis that are independent of its well-characterized functions during mitotic divisions.

730 THE ROLE OF JARID1A IN SPERMATOGENESIS EVALUATION OF TRANSCRIPTIONAL REGULATION BY HISTONE H3K4 METHYLATION

2012 ◽  
Vol 187 (4S) ◽  
Author(s):  
Hidenori Nishio ◽  
Yoshiyuki Kojima ◽  
Yoshinobu Moritoki ◽  
Makoto Imura ◽  
Hideyuki Kamisawa ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
H3k4 Methylation ◽  
Histone H3k4

Questions on the role of biofilms for the adaptation of microorganisms to unfavorable environmental factors by the example of P. aeruginosa

2020 ◽  
Vol 99 (4) ◽  
pp. 379-383
Author(s):  
Vasily N. Afonyushkin ◽  
N. A. Donchenko ◽  
Ju. N. Kozlova ◽  
N. A. Davidova ◽  
V. Yu. Koptev ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Environmental Factors ◽  
Barrier Function ◽  
Infectious Agent ◽  
Antagonistic Activity ◽  
The Body ◽  
Main Function ◽  
Pathogenic Potential ◽  
The Face

Pseudomonas aeruginosa is a widely represented species of bacteria possessing of a pathogenic potential. This infectious agent is causing wound infections, fibrotic cystitis, fibrosing pneumonia, bacterial sepsis, etc. The microorganism is highly resistant to antiseptics, disinfectants, immune system responses of the body. The responses of a quorum sense of this kind of bacteria ensure the inclusion of many pathogenicity factors. The analysis of the scientific literature made it possible to formulate four questions concerning the role of biofilms for the adaptation of P. aeruginosa to adverse environmental factors: Is another person appears to be predominantly of a source an etiological agent or the source of P. aeruginosa infection in the environment? Does the formation of biofilms influence on the antibiotic resistance? How the antagonistic activity of microorganisms is realized in biofilm form? What is the main function of biofilms in the functioning of bacteria? A hypothesis has been put forward the effect of biofilms on the increase of antibiotic resistance of bacteria and, in particular, P. aeruginosa to be secondary in charcter. It is more likely a biofilmboth to fulfill the function of storing nutrients and provide topical competition in the face of food scarcity. In connection with the incompatibility of the molecular radii of most antibiotics and pores in biofilm, biofilm is doubtful to be capable of performing a barrier function for protecting against antibiotics. However, with respect to antibodies and immunocompetent cells, the barrier function is beyond doubt. The biofilm is more likely to fulfill the function of storing nutrients and providing topical competition in conditions of scarcity of food resources.

The Modern Aristotle: Michael Polanyi’s Search for Truth against Nihilism

2018 ◽  
Author(s):  
Ronald Hoinski ◽  
Ronald Polansky
Keyword(s):  
Philosophy Of Science ◽  
Modern Science ◽  
Michael Polanyi ◽  
Contemporary Philosophy ◽  
The Face ◽  
Human Desire ◽  
The Mind ◽  
Theoretical Science

David Hoinski and Ronald Polansky’s “The Modern Aristotle: Michael Polanyi’s Search for Truth against Nihilism” shows how the general tendencies of contemporary philosophy of science disclose a return to the Aristotelian emphasis on both the formation of dispositions to know and the role of the mind in theoretical science. Focusing on a comparison of Michael Polanyi and Aristotle, Hoinski and Polansky investigate to what degree Aristotelian thought retains its purchase on reality in the face of the changes wrought by modern science. Polanyi’s approach relies on several Aristotelian assumptions, including the naturalness of the human desire to know, the institutional and personal basis for the accumulation of knowledge, and the endorsement of realism against objectivism. Hoinski and Polansky emphasize the promise of Polanyi’s neo-Aristotelian framework, which argues that science is won through reflection on reality.

Expansion of borders in the Kurdistan region and local and regional positions

2019 ◽  
Vol 3 (11) ◽  
pp. 1
Author(s):  
Harith Qahtan Abdullah ◽  
Abbas Fadel Atwan
Keyword(s):  
Middle East ◽  
Central Government ◽  
Kurdistan Region ◽  
War On Terrorism ◽  
National State ◽  
The Face ◽  
In The Beginning

The borders of Kurdistan represent an important point in Kurdish thought. They represent the hope of establishing their national state. The circumstances of the war on terrorism in Iraq and Syria have led to the emergence of what is known as a "propaganda" and the formation of a global front in its struggle. And with the signs of the collapse of the Syrian state and the weakness of the Iraqi state in the face of the "dashing" in the beginning. These circumstances led to the emergence of the role of the Kurdistan region in the confrontation "ISIS" and maintain the administrative border in the three provinces of Kurdistan in addition to the province of Kirkuk. That the circumstances of the war on terrorism created new international conditions on the Middle East arena, which will generate many problems between the Kurdistan region and the central government of Baghdad, as well as other problems between the region, Syria, Turkey and Iran. The war on terrorism has made countries free to fight the opposition groups under the name Terrorism by their classification. The Turkish side is fighting the PKK within the borders of the Kurdistan region, and this war can develop in a post-"warlike" phase. The war in Syria is also contradictory to vision and not resolved to a specific side and Iran's position on developments is encouraging.

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