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

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.

2016 ◽  
Vol 94 (5) ◽  
pp. 480-490 ◽  
Author(s):  
Ciro Rivera-Casas ◽  
Rodrigo González-Romero ◽  
Ángel Vizoso-Vazquez ◽  
Manjinder S. Cheema ◽  
M. Esperanza Cerdán ◽  
...  

Histones are the fundamental constituents of the eukaryotic chromatin, facilitating the physical organization of DNA in chromosomes and participating in the regulation of its metabolism. The H2A family displays the largest number of variants among core histones, including the renowned H2A.X, macroH2A, H2A.B (Bbd), and H2A.Z. This latter variant is especially interesting because of its regulatory role and its differentiation into 2 functionally divergent variants (H2A.Z.1 and H2A.Z.2), further specializing the structure and function of vertebrate chromatin. In the present work we describe, for the first time, the presence of a second H2A.Z variant (H2A.Z.2) in the genome of a non-vertebrate animal, the mussel Mytilus. The molecular and evolutionary characterization of mussel H2A.Z.1 and H2A.Z.2 histones is consistent with their functional specialization, supported on sequence divergence at promoter and coding regions as well as on varying gene expression patterns. More precisely, the expression of H2A.Z.2 transcripts in gonadal tissue and its potential upregulation in response to genotoxic stress might be mirroring the specialization of this variant in DNA repair. Overall, the findings presented in this work complement recent reports describing the widespread presence of other histone variants across eukaryotes, supporting an ancestral origin and conserved role for histone variants in chromatin.


2020 ◽  
Vol 54 (1) ◽  
pp. 121-149 ◽  
Author(s):  
Benjamin Loppin ◽  
Frédéric Berger

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.


2021 ◽  
Vol 55 (S3) ◽  
pp. 65-86

The family of two-pore domain potassium (K2P) channels is critically involved in central cellular functions such as ion homeostasis, cell development, and excitability. K2P channels are widely expressed in different human cell types and organs. It is therefore not surprising that aberrant expression and function of K2P channels are related to a spectrum of human diseases, including cancer, autoimmune, CNS, cardiovascular, and urinary tract disorders. Despite homologies in structure, expression, and stimulus, the functional diversity of K2P channels leads to heterogeneous influences on human diseases. The role of individual K2P channels in different disorders depends on expression patterns and modulation in cellular functions. However, an imbalance of potassium homeostasis and action potentials contributes to most disease pathologies. In this review, we provide an overview of current knowledge on the role of K2P channels in human diseases. We look at altered channel expression and function, the potential underlying molecular mechanisms, and prospective research directions in the field of K2P channels.


2019 ◽  
Author(s):  
Martina Dori ◽  
Leila Haj Abdullah Alieh ◽  
Daniel Cavalli ◽  
Simone Massalini ◽  
Mathias Lesche ◽  
...  

ABSRTRACTCircular (circ) RNAs have recently emerged as a novel class of non coding transcripts whose identification and function remain elusive. Among many tissues and species, the mammalian brain is the organ in which circRNAs are more abundant and first evidence of their functional significance started to emerge. Yet, even within this well studied organ, annotation of circRNAs remains fragmentary, their sequence is unknown and their expression in specific cell types was never investigated. Overcoming these limitations, here we provide the fist comprehensive identification of circRNAs and their expression patterns in proliferating neural stem cells, neurogenic progenitors and newborn neurons of the developing mouse cortex. Extending the current knowledge about the diversity of this class of transcripts by the identification of nearly 4,000 new circRNAs, our study is the first to provide the full sequence information and expression patterns of circRNAs in cell types representing the lineage of neurogenic commitment. We further exploited our data by evaluating the coding potential, evolutionary conservation and biogenesis of circRNAs that we found to arise from a specific sub-class of linear mRNAs. Our study provides the arising field of circRNA biology with a powerful new resource to address the complexity and potential biological significance of this new class of transcripts.


2011 ◽  
Vol 2011 ◽  
pp. 1-27 ◽  
Author(s):  
Kemal Ugur Tufekci ◽  
Meryem Gulfem Oner ◽  
Sermin Genc ◽  
Kursad Genc

MicroRNAs (miRNAs) have recently emerged as a new class of modulators of gene expression. miRNAs control protein synthesis by targeting mRNAs for translational repression or degradation at the posttranscriptional level. These noncoding RNAs are endogenous, single-stranded molecules approximately 22 nucleotides in length and have roles in multiple facets of immunity, from regulation of development of key cellular players to activation and function in immune responses. Recent studies have shown that dysregulation of miRNAs involved in immune responses leads to autoimmunity. Multiple sclerosis (MS) serves as an example of a chronic and organ-specific autoimmune disease in which miRNAs modulate immune responses in the peripheral immune compartment and the neuroinflammatory process in the brain. For MS, miRNAs have the potential to serve as modifying drugs. In this review, we summarize current knowledge of miRNA biogenesis and mode of action and the diverse roles of miRNAs in modulating the immune and inflammatory responses. We also review the role of miRNAs in autoimmunity, focusing on emerging data regarding miRNA expression patterns in MS. Finally, we discuss the potential of miRNAs as a disease marker and a novel therapeutic target in MS. Better understanding of the role of miRNAs in MS will improve our knowledge of the pathogenesis of this disease.


Genome ◽  
2020 ◽  
pp. 1-10
Author(s):  
Dongbo Ding ◽  
Thi Thuy Nguyen ◽  
Matthew Y.H. Pang ◽  
Toyotaka Ishibashi

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.


Author(s):  
E. Martínez-Martínez ◽  
R. Jurado-López ◽  
P. Cervantes-Escalera ◽  
V. Cachofeiro ◽  
M. Miana

AbstractObesity and excess of adipose tissue are associated with the development of cardiovascular risk factors such as diabetes, hypertension, and hyperlipidemia. At the cardiac level, various morphological adaptations in cardiac structure and function occur in obese individuals. Different mechanisms linking obesity to these modifications have been postulated. Adipose tissue and epicardial fat releases a large number of cytokines and bioactive mediators such as leptin. Leptin circulates in proportion to body fat mass, thus serving as a satiety signal and informing central metabolic control centers as to the status of peripheral energy stores. It participates in numerous other functions both peripherally and centrally, as indicated by the wide distribution of leptin and the different isoforms of its receptor in different tissues including the heart. This hormone has distinct effects on the reproductive, cardiovascular, and immune systems; however, its role in the heart could mediate wide physiological effects observed in obese individuals. Oxidative stress is associated with obesity and may be considered to be a unifying mechanism in the development of obesity-related comorbidities. It has been reported that obesity may induce systemic oxidative stress; in turn, oxidative stress is associated with an irregular production of adipokines. We herein review the current knowledge of cardiac effects of leptin and the possible mechanisms that are involved, including oxidative stress that plays a major role in the development of cardiovascular damage.


Insects ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 254
Author(s):  
Zhengke Peng ◽  
Jun Ren ◽  
Qi Su ◽  
Yang Zeng ◽  
Lixia Tian ◽  
...  

Chitinases are of great importance in chitin degradation and remodeling in insects. However, the genome-wide distribution of chitinase-like gene family in Bemsia tabaci, a destructive pest worldwide, is still elusive. With the help of bioinformatics, we annotated 14 genes that encode putative chitinase-like proteins, including ten chitinases (Cht), three imaginal disk growth factors (IDGF), and one endo-β-N-acetylglucosaminidase (ENGase) in the genome of the whitefly, B. tabaci. These genes were phylogenetically grouped into eight clades, among which 13 genes were classified in the glycoside hydrolase family 18 groups and one in the ENGase group. Afterwards, developmental expression analysis suggested that BtCht10, BtCht5, and BtCht7 were highly expressed in nymphal stages and exhibit similar expression patterns, implying their underlying role in nymph ecdysis. Notably, nymphs exhibited a lower rate of survival when challenged by dsRNA targeting these three genes via a nanomaterial-promoted RNAi method. In addition, silencing of BtCht10 significantly resulted in a longer duration of development compared to control nymphs. These results indicate a key role of BtCht10, BtCht5, and BtCht7 in B. tabaci nymph molting. Our research depicts the differences of chitinase-like family genes in structure and function and identified potential targets for RNAi-based whitefly management.


2021 ◽  
Author(s):  
Frank J Dekker ◽  
Martijn Zwinderman ◽  
Thamar Jessurun Lobo ◽  
Petra Van der Wouden ◽  
Diana C.J. Spierings ◽  
...  

Following DNA replication, equal amounts of histones are distributed over sister chromatids by re-deposition of parental histones and deposition of newly synthesized histones. Molecular mechanisms balancing the allocation of new and old histones remain largely unknown. Here, we studied the genome-wide distribution of new histones relative to parental DNA template strands and replication initiation zones using double-click-seq. In control conditions, new histones were preferentially found on DNA replicated by the lagging strand machinery. Strikingly, replication stress induced by hydroxyurea or curaxin treatment, and inhibition of ATR or p53 inactivation, inverted the observed histone deposition bias to the strand replicated by the leading strand polymerase in line with previously reported effects on RPA occupancy. We propose that asymmetric deposition of newly synthesized histones onto sister chromatids reflects differences in the processivity of leading and lagging strand synthesis.


2021 ◽  
Author(s):  
Isabel Cristina Velez-Bermudez ◽  
Wolfgang Schmidt

Covalent modifications of core histones govern downstream DNA-templated processes such as transcription by altering chromatin structure and function. Previously, we reported that the plant homeodomain protein ALFIN-LIKE 6 (AL6), a bona fide histone reader that preferentially binds trimethylated lysin 4 on histone 3 (H3K4me3), is critical for recalibration of cellular phosphate (Pi) homeostasis and root hair elongation under Pi-deficient conditions. Here, we demonstrate that AL6 is also involved in the response of Arabidopsis seedlings to jasmonic acid (JA) during skotomorphogenesis, possibly by modulating chromatin dynamics that affect the transcriptional regulation of JA-responsive genes. Dark-grown al6 seedlings showed a compromised reduction in hypocotyl elongation upon exogenously supplied JA, a response that was calibrated by the availability of Pi in the growth medium. A comparison of protein profiles between wild-type and al6 mutant seedlings using a quantitative Chromatin Enrichment for Proteomics (ChEP) approach, that we modified for plant tissue and designated ChEP-P (ChEP in Plants), yielded a comprehensive suite of chromatin-associated proteins and candidates that may be causative for the mutant phenotype. Altered abundance of proteins involved in chromatin organization in al6 seedlings suggests a role of AL6 in coordinating the deposition of histone variants upon perception of internal or environmental stimuli.


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