Histone Variants: The Nexus of Developmental Decisions and Epigenetic Memory

2020 ◽  
Vol 54 (1) ◽  
pp. 121-149 ◽  
Author(s):  
Benjamin Loppin ◽  
Frédéric Berger
Keyword(s):  
Cell Differentiation ◽  
Cell Fate ◽  
Histone Variants ◽  
Epigenetic Memory ◽  
The Core ◽  
Nucleosome Dynamics ◽  
Nucleosome Structure ◽  
Core Histones ◽  
And Function ◽  
The Impact

Nucleosome dynamics and properties are central to all forms of genomic activities. Among the core histones, H3 variants play a pivotal role in modulating nucleosome structure and function. Here, we focus on the impact of H3 variants on various facets of development. The deposition of the replicative H3 variant following DNA replication is essential for the transmission of the epigenomic information encoded in posttranscriptional modifications. Through this process, replicative H3 maintains cell fate while, in contrast, the replacement H3.3 variant opposes cell differentiation during early embryogenesis. In later steps of development, H3.3 and specialized H3 variants are emerging as new, important regulators of terminal cell differentiation, including neurons and gametes. The specific pathways that regulate the dynamics of the deposition of H3.3 are paramount during reprogramming events that drive zygotic activation and the initiation of a new cycle of development.

scholarly journals Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act as Important Regulators of Lymphatic Development and Function

2021 ◽  
Vol 22 (8) ◽  
pp. 3955
Author(s):  
László Bálint ◽  
Zoltán Jakus
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Mechanical Forces ◽  
Lymphatic Endothelial Cells ◽  
Lymphatic Development ◽  
And Function ◽  
The Impact

Our understanding of the function and development of the lymphatic system is expanding rapidly due to the identification of specific molecular markers and the availability of novel genetic approaches. In connection, it has been demonstrated that mechanical forces contribute to the endothelial cell fate commitment and play a critical role in influencing lymphatic endothelial cell shape and alignment by promoting sprouting, development, maturation of the lymphatic network, and coordinating lymphatic valve morphogenesis and the stabilization of lymphatic valves. However, the mechanosignaling and mechanotransduction pathways involved in these processes are poorly understood. Here, we provide an overview of the impact of mechanical forces on lymphatics and summarize the current understanding of the molecular mechanisms involved in the mechanosensation and mechanotransduction by lymphatic endothelial cells. We also discuss how these mechanosensitive pathways affect endothelial cell fate and regulate lymphatic development and function. A better understanding of these mechanisms may provide a deeper insight into the pathophysiology of various diseases associated with impaired lymphatic function, such as lymphedema and may eventually lead to the discovery of novel therapeutic targets for these conditions.

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.

scholarly journals Role of Histone N-Terminal Tails and Their Acetylation in Nucleosome Dynamics

2000 ◽  
Vol 20 (19) ◽  
pp. 7230-7237 ◽  
Author(s):  
Violette Morales ◽  
Hélène Richard-Foy
Keyword(s):  
Topoisomerase I ◽  
Globular Domain ◽  
Histone Tail ◽  
Histone Tails ◽  
Nucleosome Dynamics ◽  
Nucleosome Structure ◽  
Left Handed ◽  
Negative Supercoiling ◽  
And Function

ABSTRACT Histone N-terminal tails are central to the processes that modulate nucleosome structure and function. We have studied the contribution of core histone tails to the structure of a single nucleosome and to a histone (H3-H4)2 tetrameric particle assembled on a topologically constrained DNA minicircle. The effect of histone tail cleavage and histone tail acetylation on the structure of the nucleoprotein particle was investigated by analyzing the DNA topoisomer equilibrium after relaxation of DNA torsional stress by topoisomerase I. Removal of the H3 and H4 N-terminal tails, as well as their acetylation, provoked a dramatic change in the linking-number difference of the (H3-H4)2 tetrameric particle, with a release of up to 70% of the negative supercoiling previously constrained by this structure. The (H3-H4)2 tetramers containing tailless or hyperacetylated histones showed a striking preference for relaxed DNA over negatively supercoiled DNA. This argues in favor of a change in tetramer structure that constrains less DNA and adopts a relaxed flat conformation instead of its left-handed conformation within the nucleosome. In contrast neither removal or hyperacetylation of H3 and H4 tails nor removal or hyperacetylation of H2A and H2B N-terminal tails affected the nucleosome structure. This indicates that the globular domain of H2A and H2B is sufficient to stabilize the tailless or the hyperacetylated (H3-H4)2tetramer in a left-handed superhelix conformation. These results suggest that the effect of histone tail acetylation that facilitates transcription may be mediated via transient formation of an (H3-H4)2 tetrameric particle that could adopt an open structure only when H3 and/or H4 tails are hyperacetylated.

scholarly journals Short Histone H2A Variants: Small in Stature but not in Function

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 867 ◽  
Author(s):  
Xuanzhao Jiang ◽  
Tatiana A. Soboleva ◽  
David J. Tremethick
Keyword(s):  
Chromatin Structure ◽  
Biochemical Composition ◽  
Histone Variants ◽  
Histone H2a ◽  
The Core ◽  
Unique Protein ◽  
Core Histones ◽  
The Brain ◽  
Fundamental Mechanism ◽  
The Way

The dynamic packaging of DNA into chromatin regulates all aspects of genome function by altering the accessibility of DNA and by providing docking pads to proteins that copy, repair and express the genome. Different epigenetic-based mechanisms have been described that alter the way DNA is organised into chromatin, but one fundamental mechanism alters the biochemical composition of a nucleosome by substituting one or more of the core histones with their variant forms. Of the core histones, the largest number of histone variants belong to the H2A class. The most divergent class is the designated “short H2A variants” (H2A.B, H2A.L, H2A.P and H2A.Q), so termed because they lack a H2A C-terminal tail. These histone variants appeared late in evolution in eutherian mammals and are lineage-specific, being expressed in the testis (and, in the case of H2A.B, also in the brain). To date, most information about the function of these peculiar histone variants has come from studies on the H2A.B and H2A.L family in mice. In this review, we describe their unique protein characteristics, their impact on chromatin structure, and their known functions plus other possible, even non-chromatin, roles in an attempt to understand why these peculiar histone variants evolved in the first place.

scholarly journals Similar yet critically different: the distribution, dynamics and function of histone variants

2020 ◽  
Vol 71 (17) ◽  
pp. 5191-5204 ◽  
Author(s):  
Aline V Probst ◽  
Bénédicte Desvoyes ◽  
Crisanto Gutierrez
Keyword(s):  
Current Knowledge ◽  
Specific Binding ◽  
Expression Patterns ◽  
Histone Variants ◽  
Wide Distribution ◽  
Core Histones ◽  
Dynamics And Function ◽  
And Function ◽  
Histone Deposition ◽  
Dna Template

Abstract Organization of the genetic information into chromatin plays an important role in the regulation of all DNA template-based reactions. The incorporation of different variant versions of the core histones H3, H2A, and H2B, or the linker histone H1 results in nucleosomes with unique properties. Histone variants can differ by only a few amino acids or larger protein domains and their incorporation may directly affect nucleosome stability and higher order chromatin organization or indirectly influence chromatin function through histone variant-specific binding partners. Histone variants employ dedicated histone deposition machinery for their timely and locus-specific incorporation into chromatin. Plants have evolved specific histone variants with unique expression patterns and features. In this review, we discuss our current knowledge on histone variants in Arabidopsis, their mode of deposition, variant-specific post-translational modifications, and genome-wide distribution, as well as their role in defining different chromatin states.

scholarly journals Ezh2 regulates differentiation and function of natural killer cells through histone methyltransferase activity

2015 ◽  
Vol 112 (52) ◽  
pp. 15988-15993 ◽  
Author(s):  
Jie Yin ◽  
Jianmei W. Leavenworth ◽  
Yang Li ◽  
Qi Luo ◽  
Huafeng Xie ◽  
...  
Keyword(s):  
Natural Killer ◽  
Cell Fate ◽  
Nk Cell ◽  
Cell Lineage ◽  
Hematopoietic Stem ◽  
Lectin Receptor ◽  
Positive Effects ◽  
Cell Commitment ◽  
And Function ◽  
The Impact

Changes of histone modification status at critical lineage-specifying gene loci in multipotent precursors can influence cell fate commitment. The contribution of these epigenetic mechanisms to natural killer (NK) cell lineage determination from common lymphoid precursors is not understood. Here we investigate the impact of histone methylation repressive marks (H3 Lys27 trimethylation; H3K27me3) on early NK cell differentiation. We demonstrate that selective loss of the histone-lysine N-methyltransferase Ezh2 (enhancer of zeste homolog 2) or inhibition of its enzymatic activity with small molecules unexpectedly increased generation of the IL-15 receptor (IL-15R) CD122+ NK precursors and mature NK progeny from both mouse and human hematopoietic stem and progenitor cells. Mechanistic studies revealed that enhanced NK cell expansion and cytotoxicity against tumor cells were associated with up-regulation of CD122 and the C-type lectin receptor NKG2D. Moreover, NKG2D deficiency diminished the positive effects of Ezh2 inhibitors on NK cell commitment. Identification of the contribution of Ezh2 to NK lineage specification and function reveals an epigenetic-based mechanism that regulates NK cell development and provides insight into the clinical application of Ezh2 inhibitors in NK-based cancer immunotherapies.

scholarly journals Epigenetic regulation of the histone-to-protamine transition during spermiogenesis

Reproduction ◽  
2016 ◽  
Vol 151 (5) ◽  
pp. R55-R70 ◽  
Author(s):  
Jianqiang Bao ◽  
Mark T Bedford
Keyword(s):  
Transcription Factors ◽  
Germ Cells ◽  
Transition Process ◽  
Histone Variants ◽  
Motile Sperm ◽  
Male Germ Cells ◽  
The Core ◽  
Developmental Program ◽  
Core Histones ◽  
Epigenetic Regulators

Abstract In mammals, male germ cells differentiate from haploid round spermatids to flagella-containing motile sperm in a process called spermiogenesis. This process is distinct from somatic cell differentiation in that the majority of the core histones are replaced sequentially, first by transition proteins and then by protamines, facilitating chromatin hyper-compaction. This histone-to-protamine transition process represents an excellent model for the investigation of how epigenetic regulators interact with each other to remodel chromatin architecture. Although early work in the field highlighted the critical roles of testis-specific transcription factors in controlling the haploid-specific developmental program, recent studies underscore the essential functions of epigenetic players involved in the dramatic genome remodeling that takes place during wholesale histone replacement. In this review, we discuss recent advances in our understanding of how epigenetic players, such as histone variants and histone writers/readers/erasers, rewire the haploid spermatid genome to facilitate histone substitution by protamines in mammals.

209. The absence of betaglycan affects Sox9 m RNA expression at the time of sex determination in a mouse model

2008 ◽  
Vol 20 (9) ◽  
pp. 9
Author(s):  
M. A. Sarraj ◽  
H. Chua ◽  
A. Umbers ◽  
R. Escalona ◽  
K. L. Loveland ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Sex Determination ◽  
Sertoli Cell ◽  
Leydig Cell ◽  
Cell Biology ◽  
Leydig Cells ◽  
Cell Marker ◽  
Sox9 Expression ◽  
And Function ◽  
The Impact

Betaglycan is a co-receptor that binds both TGF-β and inhibin, and thereby acts as a modulator of the activities of multiple members of the TGF-β superfamily. We have previously shown that the murine betaglycan gene is expressed in somatic cells within the interstitium of the fetal testis from 12.5 dpc-16.5 dpc. Betaglycan protein was predominantly localised to the interstitial cells surrounding the developing seminiferous cords which stained positive for Cyp11a (p450 Scc), a Leydig cell marker. In order to determine the impact of this receptor on fetal Leydig cell biology, RNA was extracted from two independently collected sets of betaglycan knockout and wildtype male and female gonads at 12.5 dpc and 13.5 dpc (n = 4 gonad pairs/set), and quantitative real time PCR was performed to determine changes in the expression levels of key genes involved in fetal Leydig cell differentiation and function. This analysis revealed that the levels of mRNA expression of SF1, Cyp11a and Cyp17a1 were downregulated between 12.5–13.5 dpc in the betaglycan knockout embryos compared with wildtype embryos immediately after the time of sex determination. Interestingly, the expression level of the key Sertoli cell marker SRY-(sex determining region Y)-box 9 (Sox9) was transiently decreased at 12.5 dpc by 50% in the knockout testis in comparison with that of the wildtype testis. No significant change was found one day later at 13.5 dpc. Our data show that betaglycan is predominantly expressed in the fetal Leydig cells of the murine testis and that the presence of this receptor is required for normal fetal Leydig cell differentiation. Furthermore, the transient downregulation of Sox9 expression in null testis suggests that Sertoli cell differentiation may also be affected in betaglycan knockout mice, and that this defect may precede the defect in Leydig cell development. Supported by: the NHMRC Australia (RegKeys 338516; 241000).

Primate-specific histone variants

Genome ◽  
2020 ◽  
pp. 1-10
Author(s):  
Dongbo Ding ◽  
Thi Thuy Nguyen ◽  
Matthew Y.H. Pang ◽  
Toyotaka Ishibashi
Keyword(s):  
Dna Repair ◽  
Genomic Dna ◽  
Expression Profiles ◽  
Histone Variants ◽  
Amino Acid Sequences ◽  
Specific Expression ◽  
Linker Histones ◽  
Cellular Processes ◽  
Core Histones ◽  
And Function

Canonical histones (H2A, H2B, H3, and H4) are present in all eukaryotes where they package genomic DNA and participate in numerous cellular processes, such as transcription regulation and DNA repair. In addition to the canonical histones, there are many histone variants, which have different amino acid sequences, possess tissue-specific expression profiles, and function distinctly from the canonical counterparts. A number of histone variants, including both core histones (H2A/H2B/H3/H4) and linker histones (H1/H5), have been identified to date. Htz1 (H2A.Z) and CENP-A (CenH3) are present from yeasts to mammals, and H3.3 is present from Tetrahymena to humans. In addition to the prevalent variants, others like H3.4 (H3t), H2A.Bbd, and TH2B, as well as several H1 variants, are found to be specific to mammals. Among them, H2BFWT, H3.5, H3.X, H3.Y, and H4G are unique to primates (or Hominidae). In this review, we focus on localization and function of primate- or hominidae-specific histone variants.

scholarly journals Transglutaminase Regulation of Cell Function

2014 ◽  
Vol 94 (2) ◽  
pp. 383-417 ◽  
Author(s):  
Richard L. Eckert ◽  
Mari T. Kaartinen ◽  
Maria Nurminskaya ◽  
Alexey M. Belkin ◽  
Gozde Colak ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Differentiation ◽  
Cell Fate ◽  
Mechanism Of Action ◽  
Cell Function ◽  
Cellular Systems ◽  
Cancer Development ◽  
Disease States ◽  
Wide Range ◽  
And Function

Transglutaminases (TGs) are multifunctional proteins having enzymatic and scaffolding functions that participate in regulation of cell fate in a wide range of cellular systems and are implicated to have roles in development of disease. This review highlights the mechanism of action of these proteins with respect to their structure, impact on cell differentiation and survival, role in cancer development and progression, and function in signal transduction. We also discuss the mechanisms whereby TG level is controlled and how TGs control downstream targets. The studies described herein begin to clarify the physiological roles of TGs in both normal biology and disease states.

Sign in / Sign up

Export Citation Format

Share Document