scholarly journals Proteasome activator PA200 maintains stability of histone marks during transcription and aging

2020 ◽  
Author(s):  
Tian-Xia Jiang ◽  
Shuang Ma ◽  
Xia Han ◽  
Zi-Yu Luo ◽  
Qian-Qian Zhu ◽  
...  
Keyword(s):  
Epigenetic Inheritance ◽  
Cellular Aging ◽  
Dependent Manner ◽  
Histone Marks ◽  
Proteasome Activator ◽  
The Core ◽  
Degradation Rates ◽  
Transcription Inhibitor ◽  
Core Histones ◽  
The Stability

AbstractThe epigenetic inheritance relies on stability of histone marks, but various diseases, including aging-related diseases, are usually associated with alterations of histone marks. How the stability of histone marks is maintained still remains unclear. The core histones can be degraded by the atypical proteasome, which contains the proteasome activator PA200, in an acetylation-dependent manner during somatic DNA damage response and spermiogenesis. Here we show that PA200 promotes the transcription-coupled degradation of the core histones, and plays an important role in maintaining the stability of histone marks. Degradation of the histone variant H3.3, which is incorporated into chromatin during transcription, was much faster than that of its canonical form H3.1, which is incorporated during DNA replication. This degradation of the core histones could be suppressed by the transcription inhibitor, the proteasome inhibitor or deletion of PA200. The histone deacetylase inhibitor accelerated the degradation rates of H3 in general, especially its variant H3.3, while the mutations of the putative acetyl-lysine-binding region of PA200 abolished histone degradation in the G1-arrested cells, supporting that acetylation is involved in the degradation of the core histones. Deletion of PA200 dramatically altered deposition of the active transcriptional hallmarks (H3K4me3 and H3K56ac) and transcription, especially during cellular aging. Furthermore, deletion of PA200 or its yeast ortholog Blm10 accelerated cellular aging. Notably, the PA200-deficient mice displayed a range of aging-related deteriorations, including immune malfunction, anxiety-like behaviors and shorter lifespan. Thus, the proteasome activator PA200 is critical to the maintenance of the stability of histone marks during transcription and aging.

Proteasome activator Blm10 regulates transcription especially during aging

2021 ◽  
Vol 22 ◽  
Author(s):  
Yu-Shan Chen ◽  
Xia Han ◽  
Kui Lin ◽  
Tian-Xia Jiang ◽  
Xiao-Bo Qiu
Keyword(s):  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Cellular Aging ◽  
Yeast Cells ◽  
Histone Marks ◽  
Proteasome Activator ◽  
The Core ◽  
Core Histones ◽  
The Stability

Background: Histones are basic elements of the chromatin, and are critical to controlling chromatin structure and transcription. The proteasome activator PA200 promotes the acetylation-dependent proteasomal degradation of the core histones during spermatogenesis, DNA repair, transcription and cellular aging, and maintains the stability of histone marks. Objective: The study aimed to explore whether the yeast ortholog of PA200, Blm10, promotes degradation of the core histones during transcription and regulates transcription especially during aging. Method: Protein degradation assays were performed to detect the role of Blm10 in histone degradation during transcription. mRNA profiles were compared in WT and mutant BY4741 or MDY510 yeast cells by RNA-sequencing. Results: The core histones can be degraded by the Blm10-proteasome in the non-replicating yeast, suggesting that Blm10 promotes the transcription-coupled degradation of the core histones. Blm10 preferentially regulates transcription in aged yeast, especially transcription of genes related to translation, amino acid metabolism and carbohydrate metabolism. Mutations of Blm10 at F2125/N2126 in its putative acetyl-lysine binding region abolished the Blm10-mediated regulation of gene expression. Conclusion: Blm10 promotes degradation of the core histones during transcription and regulates transcription especially during cellular aging, further supporting the critical role of PA200 in maintaining the stability of histone marks from the evolutionary view. These results should provide meaningful insights into the mechanisms underlying aging and the related diseases.

Thermodynamic Studies of the Core Histones:  pH and Ionic Strength Effects on the Stability of the (H3−H4)/(H3−H4)2System†

Biochemistry ◽  
1996 ◽  
Vol 35 (6) ◽  
pp. 2037-2046 ◽  
Author(s):  
Vassiliki Karantza ◽  
Ernesto Freire ◽  
Evangelos N. Moudrianakis
Keyword(s):  
Ionic Strength ◽  
Thermodynamic Studies ◽  
The Core ◽  
Core Histones ◽  
The Stability

scholarly journals The Yin and Yang of Histone Marks in Transcription

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Paul B. Talbert ◽  
Steven Henikoff
Keyword(s):  
Posttranslational Modifications ◽  
Human Genetics ◽  
Annual Review ◽  
Publication Date ◽  
Histone Marks ◽  
The Core ◽  
Core Histones ◽  
Yin And Yang ◽  
Transcriptional State ◽  
Histone Core

Nucleosomes wrap DNA and impede access for the machinery of transcription. The core histones that constitute nucleosomes are subject to a diversity of posttranslational modifications, or marks, that impact the transcription of genes. Their functions have sometimes been difficult to infer because the enzymes that write and read them are complex, multifunctional proteins. Here, we examine the evidence for the functions of marks and argue that the major marks perform a fairly small number of roles in either promoting transcription or preventing it. Acetylations and phosphorylations on the histone core disrupt histone-DNA contacts and/or destabilize nucleosomes to promote transcription. Ubiquitylations stimulate methylations that provide a scaffold for either the formation of silencing complexes or resistance to those complexes, and carry a memory of the transcriptional state. Tail phosphorylations deconstruct silencing complexes in particular contexts. We speculate that these fairly simple roles form the basis of transcriptional regulation by histone marks. Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 22 is August 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Homology sensing via non-linear amplification of sequence-dependent pausing by RecQ helicase

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Yeonee Seol ◽  
Gábor M Harami ◽  
Mihály Kovács ◽  
Keir C Neuman
Keyword(s):  
Single Molecule ◽  
Magnetic Tweezers ◽  
Dependent Manner ◽  
Linear Amplification ◽  
Recq Helicases ◽  
The Core ◽  
Sequence Dependent ◽  
Non Linear ◽  
Dna Strand ◽  
The Stability

RecQ helicases promote genomic stability through their unique ability to suppress illegitimate recombination and resolve recombination intermediates. These DNA structure-specific activities of RecQ helicases are mediated by the helicase-and-RNAseD like C-terminal (HRDC) domain, via unknown mechanisms. Here, employing single-molecule magnetic tweezers and rapid kinetic approaches we establish that the HRDC domain stabilizes intrinsic, sequence-dependent, pauses of the core helicase (lacking the HRDC) in a DNA geometry-dependent manner. We elucidate the core unwinding mechanism in which the unwinding rate depends on the stability of the duplex DNA leading to transient sequence-dependent pauses. We further demonstrate a non-linear amplification of these transient pauses by the controlled binding of the HRDC domain. The resulting DNA sequence- and geometry-dependent pausing may underlie a homology sensing mechanism that allows rapid disruption of unstable (illegitimate) and stabilization of stable (legitimate) DNA strand invasions, which suggests an intrinsic mechanism of recombination quality control by RecQ helicases.

scholarly journals Human Histone Chaperone Nucleophosmin Enhances Acetylation-Dependent Chromatin Transcription

2005 ◽  
Vol 25 (17) ◽  
pp. 7534-7545 ◽  
Author(s):  
V. Swaminathan ◽  
A. Hari Kishore ◽  
K. K. Febitha ◽  
Tapas K. Kundu
Keyword(s):  
Transcriptional Activation ◽  
Histone Chaperone ◽  
Dependent Manner ◽  
Histone Chaperones ◽  
Cellular Processes ◽  
The Core ◽  
Core Histones ◽  
Nucleosomal Structure

ABSTRACT Histone chaperones are a group of proteins that aid in the dynamic chromatin organization during different cellular processes. Here, we report that the human histone chaperone nucleophosmin interacts with the core histones H3, H2B, and H4 but that this histone interaction is not sufficient to confer the chaperone activity. Significantly, nucleophosmin enhances the acetylation-dependent chromatin transcription and it becomes acetylated both in vitro and in vivo. Acetylation of nucleophosmin and the core histones was found to be essential for the enhancement of chromatin transcription. The acetylated NPM1 not only shows an increased affinity toward acetylated histones but also shows enhanced histone transfer ability. Presumably, nucleophosmin disrupts the nucleosomal structure in an acetylation-dependent manner, resulting in the transcriptional activation. These results establish nucleophosmin (NPM1) as a human histone chaperone that becomes acetylated, resulting in the enhancement of chromatin transcription.

scholarly journals Structural and dynamic mechanisms of CBF3-guided centromeric nucleosome formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ruifang Guan ◽  
Tengfei Lian ◽  
Bing-Rui Zhou ◽  
Emily He ◽  
Carl Wu ◽  
...  
Keyword(s):  
Dna Sequence ◽  
Chromosome Segregation ◽  
Budding Yeast ◽  
Dna Conformation ◽  
Dependent Manner ◽  
Dynamic Interactions ◽  
Nucleosome Core ◽  
Dynamic Mechanisms ◽  
Nucleosome Formation ◽  
Core Histones

AbstractAccurate chromosome segregation relies on the specific centromeric nucleosome–kinetochore interface. In budding yeast, the centromere CBF3 complex guides the deposition of CENP-A, an H3 variant, to form the centromeric nucleosome in a DNA sequence-dependent manner. Here, we determine the structures of the centromeric nucleosome containing the native CEN3 DNA and the CBF3core bound to the canonical nucleosome containing an engineered CEN3 DNA. The centromeric nucleosome core structure contains 115 base pair DNA including a CCG motif. The CBF3core specifically recognizes the nucleosomal CCG motif through the Gal4 domain while allosterically altering the DNA conformation. Cryo-EM, modeling, and mutational studies reveal that the CBF3core forms dynamic interactions with core histones H2B and CENP-A in the CEN3 nucleosome. Our results provide insights into the structure of the budding yeast centromeric nucleosome and the mechanism of its assembly, which have implications for analogous processes of human centromeric nucleosome formation.

scholarly journals Identification and Characterization of the Genes Encoding the Core Histones and Histone Variants of Neurospora crassa

Genetics ◽  
2002 ◽  
Vol 160 (3) ◽  
pp. 961-973 ◽  
Author(s):  
Shan M Hays ◽  
Johanna Swanson ◽  
Eric U Selker
Keyword(s):  
Neurospora Crassa ◽  
Histone Variants ◽  
Null Alleles ◽  
Histone Genes ◽  
Histone H4 ◽  
Coding Regions ◽  
The Core ◽  
Genomic Arrangement ◽  
Genes Encoding ◽  
Core Histones

Abstract We have identified and characterized the complete complement of genes encoding the core histones of Neurospora crassa. In addition to the previously identified pair of genes that encode histones H3 and H4 (hH3 and hH4-1), we identified a second histone H4 gene (hH4-2), a divergently transcribed pair of genes that encode H2A and H2B (hH2A and hH2B), a homolog of the F/Z family of H2A variants (hH2Az), a homolog of the H3 variant CSE4 from Saccharomyces cerevisiae (hH3v), and a highly diverged H4 variant (hH4v) not described in other species. The hH4-1 and hH4-2 genes, which are 96% identical in their coding regions and encode identical proteins, were inactivated independently. Strains with inactivating mutations in either gene were phenotypically wild type, in terms of growth rates and fertility, but the double mutants were inviable. As expected, we were unable to isolate null alleles of hH2A, hH2B, or hH3. The genomic arrangement of the histone and histone variant genes was determined. hH2Az and the hH3-hH4-1 gene pair are on LG IIR, with hH2Az centromere-proximal to hH3-hH4-1 and hH3 centromere-proximal to hH4-1. hH3v and hH4-2 are on LG IIIR with hH3v centromere-proximal to hH4-2. hH4v is on LG IVR and the hH2A-hH2B pair is located immediately right of the LG VII centromere, with hH2A centromere-proximal to hH2B. Except for the centromere-distal gene in the pairs, all of the histone genes are transcribed toward the centromere. Phylogenetic analysis of the N. crassa histone genes places them in the Euascomycota lineage. In contrast to the general case in eukaryotes, histone genes in euascomycetes are few in number and contain introns. This may be a reflection of the evolution of the RIP (repeat-induced point mutation) and MIP (methylation induced premeiotically) processes that detect sizable duplications and silence associated genes.

SHELL MATERIAL'S PERFORMANCE OF THE MICROCAPSULE FOR ELECTROLYTIC CO-DEPOSITION

2010 ◽  
Vol 24 (15n16) ◽  
pp. 3124-3130 ◽  
Author(s):  
HUI CONG LIU ◽  
XIU QING XU ◽  
WEI PING LI ◽  
YAN HONG GUO ◽  
LI-QUN ZHU
Keyword(s):  
Composite Coating ◽  
Methyl Cellulose ◽  
Water Vapor Permeability ◽  
Core Material ◽  
Vapor Permeability ◽  
Shell Material ◽  
The Core ◽  
Surface Performance ◽  
The Stability ◽  
Positive Effect

The shell material of microcapsules has an important effect on the electrolytic co-deposition behavior, the release of core material and the surface performance of composite coating. This paper discussed the tensile property and the stability of three shell materials including polyvinyl alcohol (PVA), gelatin and methyl cellulose (MC). It is found that these three shell materials have good mechanical strength and flexibility which are favorable to electrolytic co-deposition and stability of microcapsules in composite coating and that MC has well permeability and porosity which has a positive effect on the release of the core material in composite coating. Moreover, the study of the thermal properties and water vapor permeability of the three shell materials showed that their permeability improved with increase of temperature and humidity. In addition, the composite copper coating containing microcapsules with PVA, gelatin or MC as shell material was prepared respectively.

Release Profile of a Model Protein Drug Depending on the Stability of Microspheres Based on Polyelectrolyte Complex

2007 ◽  
Vol 342-343 ◽  
pp. 505-508
Author(s):  
Sung Won Kim ◽  
Yun Sik Nam ◽  
Yeon Jin Min ◽  
Jong Ho Kim ◽  
Kwang Meyong Kim ◽  
...  
Keyword(s):  
Polyelectrolyte Complex ◽  
Coating Layer ◽  
Great Influence ◽  
Release Profile ◽  
Core Material ◽  
Glycol Chitosan ◽  
The Core ◽  
Key Factor ◽  
Model Protein ◽  
The Stability

Stability and disintegration of natural polyelectrolyte complex microspheres for protein drugs delivery have been extensively investigated because of their great influence on the drug release patterns. In this study, we tested stability of microspheres with alginate (Alg) core layered by either chitosan (Chi) or glycol chitosan (GChi) by examining release profiles of fluorophorelabeled bovine serum albumin (BSA) and lysozyme (Lys) from the microspheres. While GChi shell was disintegrated quickly, Chi-shell microspheres showed good stability in PBS. Disintegration of the coated layer induced the core material instable. The results indicated that while the charges of the shell material provided additional diffusion barrier against the protein release, the key factor to hold the proteins inside the microspheres was the integrity of the outer coating layer.

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