scholarly journals Dynamic Histone H3 Modifications Regulate Meiosis Initiation via Respiration

2021 ◽  
Vol 9 ◽  
Author(s):  
Jian Shi ◽  
Yanjie Ma ◽  
Hui Hua ◽  
Yujiao Liu ◽  
Wei Li ◽  
...  
Keyword(s):  
Histone Modifications ◽  
Multiple Reaction Monitoring ◽  
Histone H3 ◽  
Negative Regulator ◽  
Reaction Monitoring ◽  
Dynamic Changes ◽  
Post Translational Modifications ◽  
Yeast Strains ◽  
Yeast Meiosis ◽  
H3 Acetylation

Meiosis is essential for genetic stability and diversity during sexual reproduction in most eukaryotes. Chromatin structure and gene expression are drastically changed during meiosis, and various histone modifications have been reported to participate in this unique process. However, the dynamic of histone modifications during meiosis is still not well investigated. Here, by using multiple reaction monitoring (MRM) based LC-MS/MS, we detected dynamic changes of histone H3 lysine post-translational modifications (PTMs). We firstly quantified the precise percentage of H3 modifications on different lysine sites during mouse and yeast meiosis, and found H3 acetylation and methylation were dramatically changed. To further study the potential functions of H3 acetylation and methylation in meiosis, we performed histone H3 lysine mutant screening in yeast, and found that yeast strains lacking H3K18 acetylation (H3K18ac) failed to initiate meiosis due to insufficient IME1 expression. Further studies showed that the absence of H3K18ac impaired respiration, leading to the reduction of Rim101p, which further upregulated a negative regulator of IME1 transcription, Smp1p. Together, our studies reveal a novel meiosis initiation pathway mediated by histone H3 modifications.

scholarly journals The chromatin-binding protein HMGN3 stimulates histone acetylation and transcription across the Glyt1 gene

2012 ◽  
Vol 442 (3) ◽  
pp. 495-505 ◽  
Author(s):  
Gráinne Barkess ◽  
Yuri Postnikov ◽  
Chrisanne D. Campos ◽  
Shivam Mishra ◽  
Gokula Mohan ◽  
...  
Keyword(s):  
Histone Modifications ◽  
Splice Variants ◽  
Binding Protein ◽  
Histone H3 ◽  
Camp Response Element Binding ◽  
Element Binding Protein ◽  
H3k14 Acetylation ◽  
H3 Acetylation

HMGNs are nucleosome-binding proteins that alter the pattern of histone modifications and modulate the binding of linker histones to chromatin. The HMGN3 family member exists as two splice forms, HMGN3a which is full-length and HMGN3b which lacks the C-terminal RD (regulatory domain). In the present study, we have used the Glyt1 (glycine transporter 1) gene as a model system to investigate where HMGN proteins are bound across the locus in vivo, and to study how the two HMGN3 splice variants affect histone modifications and gene expression. We demonstrate that HMGN1, HMGN2, HMGN3a and HMGN3b are bound across the Glyt1 gene locus and surrounding regions, and are not enriched more highly at the promoter or putative enhancer. We conclude that the peaks of H3K4me3 (trimethylated Lys4 of histone H3) and H3K9ac (acetylated Lys9 of histone H3) at the active Glyt1a promoter do not play a major role in recruiting HMGN proteins. HMGN3a/b binding leads to increased H3K14 (Lys14 of histone H3) acetylation and stimulates Glyt1a expression, but does not alter the levels of H3K4me3 or H3K9ac enrichment. Acetylation assays show that HMGN3a stimulates the ability of PCAF [p300/CREB (cAMP-response-element-binding protein)-binding protein-associated factor] to acetylate nucleosomal H3 in vitro, whereas HMGN3b does not. We propose a model where HMGN3a/b-stimulated H3K14 acetylation across the bodies of large genes such as Glyt1 can lead to more efficient transcription elongation and increased mRNA production.

scholarly journals Histone H3 Acetylation and H3 K4 Methylation Define Distinct Chromatin Regions Permissive for Transgene Expression

2006 ◽  
Vol 26 (17) ◽  
pp. 6357-6371 ◽  
Author(s):  
Chunhong Yan ◽  
Douglas D. Boyd
Keyword(s):  
Histone Modifications ◽  
Transgene Expression ◽  
De Novo ◽  
Histone H3 ◽  
Mammalian Genome ◽  
Chromatin Region ◽  
Histone H3 Acetylation ◽  
Transcription Activators ◽  
And Function ◽  
H3 Acetylation

ABSTRACT Histone modifications are associated with distinct transcription states and serve as heritable epigenetic markers for chromatin structure and function. While H3 K9 methylation defines condensed heterochromatin that is able to silence a nearby gene, how gene silencing within euchromatin regions is achieved remains elusive. We report here that histone H3 K4 methylation or K9/K14 acetylation defines distinct chromatin regions permissive or nonpermissive for transgene expression. A permissive chromatin region is enriched in H3 K4 methylation and H3 acetylation, while a nonpermissive region is poor in or depleted of these two histone modifications. The histone modification states of the permissive chromatin can spread to transgenic promoters. However, de novo histone H3 acetylation and H3 K4 methylation at a transgenic promoter in a nonpermissive chromatin region are stochastic, leading to variegated transgene expression. Moreover, nonpermissive chromatin progressively silences a transgene, an event that is accompanied by the reduction of H3 K4 methylation and H3 acetylation levels at the transgenic promoter. These repressive effects of nonpermissive chromatin cannot be completely countered by strong transcription activators, indicating the dominance of the chromatin effects. We therefore propose a model in which histone H3 acetylation and H3 K4 methylation localized to discrete sites in the mammalian genome mark distinct chromatin functions that dictate transgene expression or silencing.

scholarly journals Role of the CBP catalytic core in intramolecular SUMOylation and control of histone H3 acetylation

2017 ◽  
Vol 114 (27) ◽  
pp. E5335-E5342 ◽  
Author(s):  
Sangho Park ◽  
Robyn L. Stanfield ◽  
Maria A. Martinez-Yamout ◽  
H. Jane Dyson ◽  
Ian A. Wilson ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Critical Role ◽  
Histone H3 ◽  
Negative Regulator ◽  
Creb Binding Protein ◽  
Catalytic Core ◽  
Intrinsically Disordered ◽  
Histone H3 Acetylation ◽  
H3 Acetylation

The histone acetyl transferases CREB-binding protein (CBP) and its paralog p300 play a critical role in numerous cellular processes. Dysregulation of their catalytic activity is associated with several human diseases. Previous work has elucidated the regulatory mechanisms of p300 acetyltransferase activity, but it is not known whether CBP activity is controlled similarly. Here, we present the crystal structure of the CBP catalytic core encompassing the bromodomain (BRD), CH2 (comprising PHD and RING), HAT, and ZZ domains at 2.4-Å resolution. The BRD, PHD, and HAT domains form an integral structural unit to which the RING and ZZ domains are flexibly attached. The structure of the apo-CBP HAT domain is similar to that of acyl-CoA–bound p300 HAT complexes and shows that the acetyl-CoA binding site is stably formed in the absence of cofactor. The BRD, PHD, and ZZ domains interact with small ubiquitin-like modifier 1 (SUMO-1) and Ubc9, and function as an intramolecular E3 ligase for SUMOylation of the cell cycle regulatory domain 1 (CRD1) of CBP, which is located adjacent to the BRD. In vitro HAT assays suggest that the RING domain, the autoregulatory loop (AL) within the HAT domain, and the ZZ domain do not directly influence catalytic activity, whereas the BRD is essential for histone H3 acetylation in nucleosomal substrates. Several lysine residues in the intrinsically disordered AL are autoacetylated by the HAT domain. Upon autoacetylation, acetyl-K1596 (Ac-K1596) binds intramolecularly to the BRD, competing with histones for binding to the BRD and acting as a negative regulator that inhibits histone H3 acetylation.

scholarly journals Protein kinase C coordinates histone H3 phosphorylation and acetylation

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Zoulfia Darieva ◽  
Aaron Webber ◽  
Stacey Warwood ◽  
Andrew D Sharrocks
Keyword(s):  
Protein Kinase ◽  
Histone Modifications ◽  
Histone H3 ◽  
Chromatin Assembly ◽  
Critical Event ◽  
Histone Acetyl Transferase ◽  
Replicative Stress ◽  
H3 Phosphorylation ◽  
H3k56 Acetylation ◽  
H3 Acetylation

The re-assembly of chromatin following DNA replication is a critical event in the maintenance of genome integrity. Histone H3 acetylation at K56 and phosphorylation at T45 are two important chromatin modifications that accompany chromatin assembly. Here we have identified the protein kinase Pkc1 as a key regulator that coordinates the deposition of these modifications in S. cerevisiae under conditions of replicative stress. Pkc1 phosphorylates the histone acetyl transferase Rtt109 and promotes its ability to acetylate H3K56. Our data also reveal novel cross-talk between two different histone modifications as Pkc1 also enhances H3T45 phosphorylation and this modification is required for H3K56 acetylation. Our data therefore uncover an important role for Pkc1 in coordinating the deposition of two different histone modifications that are important for chromatin assembly.

scholarly journals Characterization of ASF1 and GCN5 in the ciliated protozoan tetrahymena thermophila

2021 ◽  
Author(s):  
Abdel Rahman Karsou
Keyword(s):  
Tetrahymena Thermophila ◽  
Histone H3 ◽  
Model Organism ◽  
Human Cells ◽  
Ciliated Protozoan ◽  
Yeast Saccharomyces Cerevisiae ◽  
Post Translational Modifications ◽  
Lysine Residues ◽  
Acetyl Group ◽  
H3 Acetylation

One method of regulating accessibility of DNA is chromatin remodelling via histone post-translational modifications (PTM). Adding an acetyl group to the lysine residues (K) on the core histone H3 is one of these chemical modifications. Acetylation of H3 on lysine 56 (H3K56ac) is an important histone alteration that is conserved among most if not all eukaryotes including humans. Several histone acetyl transferases (HAT) have been shown to be responsible for H3K56ac in different organisms including Gen5 and p300/CPB in human cells and Rtt109 in fungi including the yeast Saccharomyces cerevisiae. In addition the histone chaperone ASf1, is also required for these modifications in yeast and human cells. The ciliated protozoan Tetrahymena thermophila is an effective model organism for studying the function of histone PTMs in certain processes including meiosis and RNA interference. Here, I show that tGen5 has H3 acetylation activity and that tAsf1 binds Histone H3.

scholarly journals Characterization of ASF1 and GCN5 in the ciliated protozoan tetrahymena thermophila

2021 ◽  
Author(s):  
Abdel Rahman Karsou
Keyword(s):  
Tetrahymena Thermophila ◽  
Histone H3 ◽  
Model Organism ◽  
Human Cells ◽  
Ciliated Protozoan ◽  
Yeast Saccharomyces Cerevisiae ◽  
Post Translational Modifications ◽  
Lysine Residues ◽  
Acetyl Group ◽  
H3 Acetylation

One method of regulating accessibility of DNA is chromatin remodelling via histone post-translational modifications (PTM). Adding an acetyl group to the lysine residues (K) on the core histone H3 is one of these chemical modifications. Acetylation of H3 on lysine 56 (H3K56ac) is an important histone alteration that is conserved among most if not all eukaryotes including humans. Several histone acetyl transferases (HAT) have been shown to be responsible for H3K56ac in different organisms including Gen5 and p300/CPB in human cells and Rtt109 in fungi including the yeast Saccharomyces cerevisiae. In addition the histone chaperone ASf1, is also required for these modifications in yeast and human cells. The ciliated protozoan Tetrahymena thermophila is an effective model organism for studying the function of histone PTMs in certain processes including meiosis and RNA interference. Here, I show that tGen5 has H3 acetylation activity and that tAsf1 binds Histone H3.

scholarly journals A CRISPR-Cas9 based shuffle system for endogenous histone H3 and H4 combinatorial mutagenesis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Fu ◽  
Zhenglin Zhu ◽  
Geng Meng ◽  
Rijun Zhang ◽  
Yueping Zhang
Keyword(s):  
Cell Fate ◽  
Histone H3 ◽  
Point Mutations ◽  
Eukaryotic Cells ◽  
Post Translational Modifications ◽  
Cell Fate Decisions ◽  
Yeast Strains ◽  
Invaluable Tool ◽  
Multiple Copies ◽  
Combinatorial Mutagenesis

AbstractPost-translational modifications of histone proteins greatly impact gene expression and cell fate decisions in eukaryotes. To study these, it is important to develop a convenient, multiplex, and efficient method to precisely introduce mutations to histones. Because eukaryotic cells usually contain multiple copies of histone genes, it is a challenge to mutate all histones at the same time by the traditional homologous recombination method. Here, we developed a CRISPR-Cas9 based shuffle system in Saccharomyces cerevisiae, to generate point mutations on both endogenous histone H3 and H4 genes in a rapid, seamless and multiplex fashion. Using this method, we generated yeast strains containing histone triple H3–K4R–K36R–K79R mutants and histone combinatorial H3–K56Q–H4–K59A double mutants with high efficiencies (70–80%). This CRISPR-Cas9 based mutagenesis system could be an invaluable tool to the epigenetics field.

scholarly journals Dynamic Histone H3 Acetylation and Methylation at Human Cytomegalovirus Promoters during Replication in Fibroblasts

2008 ◽  
Vol 82 (19) ◽  
pp. 9525-9536 ◽  
Author(s):  
Christian Cuevas-Bennett ◽  
Thomas Shenk
Keyword(s):  
Human Cytomegalovirus ◽  
Histone Modifications ◽  
Histone H3 ◽  
Immediate Early ◽  
Early Promoter ◽  
Histone H3 Acetylation ◽  
Viral Promoters ◽  
High Level ◽  
H3 Acetylation ◽  
Major Immediate Early Promoter

ABSTRACT Human cytomegalovirus DNA is packaged in virions without histones but associates with histones upon reaching the nucleus of an infected cell. Since transcription is modulated by the interplay of histone modifications, we used chromatin immunoprecipitation to detect acetylation and methylation of histone H3 at viral promoters at different times during the viral replication cycle. Histone H3 at immediate-early promoters is acetylated at the start of infection, while it is initially methylated at early and late promoters. Acetylation at immediate-early promoters is dynamic, with a high level of activating modifications at 3 and 6 h postinfection (hpi), followed by a marked reduction at 12 hpi. All viral promoters, as well as nonpromoter regions, are modified with activating acetylations at 24 to 72 hpi. The transient reduction in histone H3 acetylation at the major immediate-early promoter depends on the cis-repressive sequence to which the UL122-coded IE2 protein binds. A mutant virus lacking this element exhibited decreased IE2 binding at the major immediate-early promoter and failed to show reduced acetylation of histone H3 residing at this promoter at 12 hpi. Our results demonstrate that cytomegalovirus chromatin undergoes dynamic, promoter-specific histone modifications early in the infectious cycle, after which the entire chromosome becomes highly acetylated.

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