Diet-induced- and genetic- obesity differentially alters male germline histones

Reproduction ◽  
2021 ◽  
Author(s):  
Sharvari S Deshpande ◽  
Nemani Harishankar ◽  
Nafisa Huseni Balasinor
Keyword(s):  
Sperm Quality ◽  
Cell Types ◽  
Chromatin Remodelers ◽  
Histone Marks ◽  
Male Subfertility ◽  
Established Risk Factor ◽  
Male Germline ◽  
Core Histones ◽  
Subsequent Effect ◽  
Environmental Causes

Obesity, an established risk factor for male subfertility or infertility, is primarily due to genetic and environmental causes. Our earlier studies have shown differential effects of high fat diet-induced- (DIO) and genetically inherited- (GIO) obesity on DNA methylation in male germline and its subsequent effect on fertility. Here, we hypothesized that the effects of DIO and GIO on histone modifications in male germline could also contribute to fertility defects. We observed that DIO affected both active (H3K4me3, H3ac, and H4ac) and repressive (H3K9me3 and H3K27me3) histone marks in testis and their cell types, whereas GIO solely altered acetylated histones. This correlated with deregulation of histone-modifying enzymes in testis of both obese groups. Further, we also observed a decrease in chromatin remodelers in testis of DIO group, which were increased in GIO group. Besides, there was an increase in core histones and a decrease in histone marks along with protamine deficiency in spermatozoa of DIO group, whereas only H3K4me3 levels were increased in spermatozoa of GIO group. Moreover, we observed alterations in the expression and enrichment patterns of a few developmental genes harbored by the active histone mark in resorbed embryos sired by the DIO rats. Together these epigenetic defects in male germline could alter sperm quality and cause fertility defects in these obese groups. Differential changes in two obese groups could also be attributed to differences in their pathophysiological variations. Our study highlights epigenetic differences between DIO and GIO in male germline and its subsequent impact on male fertility.

scholarly journals The Roles of Chromatin Accessibility in Regulating the Candida albicans White-Opaque Phenotypic Switch

2021 ◽  
Vol 7 (1) ◽  
pp. 37
Author(s):  
Mohammad N. Qasim ◽  
Ashley Valle Arevalo ◽  
Clarissa J. Nobile ◽  
Aaron D. Hernday
Keyword(s):  
Candida Albicans ◽  
Cell Fate ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Phenotypic Switching ◽  
Phenotypic Switch ◽  
Chromatin Remodelers ◽  
Environmental Signals ◽  
Cell Fate Decisions ◽  
Simple Model System

Candida albicans, a diploid polymorphic fungus, has evolved a unique heritable epigenetic program that enables reversible phenotypic switching between two cell types, referred to as “white” and “opaque”. These cell types are established and maintained by distinct transcriptional programs that lead to differences in metabolic preferences, mating competencies, cellular morphologies, responses to environmental signals, interactions with the host innate immune system, and expression of approximately 20% of genes in the genome. Transcription factors (defined as sequence specific DNA-binding proteins) that regulate the establishment and heritable maintenance of the white and opaque cell types have been a primary focus of investigation in the field; however, other factors that impact chromatin accessibility, such as histone modifying enzymes, chromatin remodelers, and histone chaperone complexes, also modulate the dynamics of the white-opaque switch and have been much less studied to date. Overall, the white-opaque switch represents an attractive and relatively “simple” model system for understanding the logic and regulatory mechanisms by which heritable cell fate decisions are determined in higher eukaryotes. Here we review recent discoveries on the roles of chromatin accessibility in regulating the C. albicans white-opaque phenotypic switch.

scholarly journals Epigenetic regulation of oligodendrocyte myelination in developmental disorders and neurodegenerative diseases

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 105 ◽  
Author(s):  
Kalen Berry ◽  
Jiajia Wang ◽  
Q. Richard Lu
Keyword(s):  
Neurodegenerative Diseases ◽  
Developmental Disorders ◽  
Cell Types ◽  
Fine Tuning ◽  
Rna Modification ◽  
Cns Injury ◽  
Key Factors ◽  
Chromatin Remodelers ◽  
The Central Nervous System ◽  
Histone Modifying Enzymes

Oligodendrocytes are the critical cell types giving rise to the myelin nerve sheath enabling efficient nerve transmission in the central nervous system (CNS). Oligodendrocyte precursor cells differentiate into mature oligodendrocytes and are maintained throughout life. Deficits in the generation, proliferation, or differentiation of these cells or their maintenance have been linked to neurological disorders ranging from developmental disorders to neurodegenerative diseases and limit repair after CNS injury. Understanding the regulation of these processes is critical for achieving proper myelination during development, preventing disease, or recovering from injury. Many of the key factors underlying these processes are epigenetic regulators that enable the fine tuning or reprogramming of gene expression during development and regeneration in response to changes in the local microenvironment. These include chromatin remodelers, histone-modifying enzymes, covalent modifiers of DNA methylation, and RNA modification–mediated mechanisms. In this review, we will discuss the key components in each of these classes which are responsible for generating and maintaining oligodendrocyte myelination as well as potential targeted approaches to stimulate the regenerative program in developmental disorders and neurodegenerative diseases.

scholarly journals In vivotissue-specific chromatin profiling inDrosophila melanogasterusing GFP-tagged nuclei

2021 ◽  
Author(s):  
Juan Jauregui-Lozano ◽  
Kimaya Bakhle ◽  
Vikki M. Weake
Keyword(s):  
Cell Types ◽  
Chromatin Accessibility ◽  
Chromatin State ◽  
Specific Cell ◽  
Histone Marks ◽  
The Many ◽  
Chromatin Profiling ◽  
Photoreceptor Neurons ◽  
Multicellular Organisms

AbstractThe chromatin landscape defines cellular identity in multicellular organisms with unique patterns of DNA accessibility and histone marks decorating the genome of each cell type. Thus, profiling the chromatin state of different cell types in an intact organism under disease or physiological conditions can provide insight into how chromatin regulates cell homeostasisin vivo. To overcome the many challenges associated with characterizing chromatin state in specific cell types, we developed an improved approach to isolateDrosophilanuclei tagged with GFP expressed under Gal4/UAS control. Using this protocol, we profiled chromatin accessibility using Omni-ATAC, and examined the distribution of histone marks using ChIP-seq and CUT&Tag in adult photoreceptor neurons. We show that the chromatin landscape of photoreceptors reflects the transcriptional state of these cells, demonstrating the quality and reproducibility of our approach for profiling the transcriptome and epigenome of specific cell types inDrosophila.

scholarly journals Accurate imputation of histone modifications using transcription

2020 ◽  
Author(s):  
Zhong Wang ◽  
Alexandra G. Chivu ◽  
Lauren A. Choate ◽  
Edward J. Rice ◽  
Donald C. Miller ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Cell Type ◽  
Active Chromatin ◽  
Histone Marks ◽  
Repressive Mark ◽  
Cell Type Specific ◽  
The Relationship ◽  
Machine Learning Tool

AbstractWe trained a sensitive machine learning tool to infer the distribution of histone marks using maps of nascent transcription. Transcription captured the variation in active histone marks and complex chromatin states, like bivalent promoters, down to single-nucleosome resolution and at an accuracy that rivaled the correspondence between independent ChIP-seq experiments. The relationship between active histone marks and transcription was conserved in all cell types examined, allowing individual labs to annotate active functional elements in mammals with similar richness as major consortia. Using imputation as an interpretative tool uncovered cell-type specific differences in how the PRC2-dependent repressive mark, H3K27me3, corresponds to transcription, and revealed that transcription initiation requires both chromatin accessibility and an active chromatin environment demonstrating that initiation is less promiscuous than previously thought.

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 The making of a muscle

2012 ◽  
Vol 34 (3) ◽  
pp. 4-11 ◽  
Author(s):  
Marta Fiorotto
Keyword(s):  
High Performance ◽  
Rubber Tree ◽  
In Vitro Study ◽  
Cell Types ◽  
Experimental Manipulation ◽  
Point Of Use ◽  
Wide Range ◽  
The Difference ◽  
Environmental Causes

The skeletal musculature is usually thought of as the primary organ of locomotion, and, like the tyres of a high-performance racing car, their composition, design, preparation and plasticity can make the difference between winner and ‘wannabe’. The similarities do not end there, however. Their primary components (cells of the mesodermal layer in the embryo and latex from the rubber tree) begin their existence in locations that can be quite distant from their final point of use and in forms that bear no resemblance to the final product. Their differentiation from primary material to final product entails extensive processing, and the integration of other materials and structures are essential to ensure their function. A fundamental difference, however, is that, in the case of muscle, once the embryo is formed, the progression from relatively undifferentiated mesodermal cells to the final structures is on autopilot, provided there are no contextual aberrations either from genetic or environmental causes. Our current understanding of how muscles develop is a synthesis of observations made on a wide array of organisms, including nematode worms, fruitflies, fish, frogs, birds and various mammals, as well as from the in vitro study of cells isolated from these species. The study of myogenesis in mammals, although less amenable to experimental manipulation, has been facilitated by the recent advances in mouse genetic engineering which has enabled the function of individual genes and cell types to be investigated, as well as the lineage of cells to be traced back to their origin. In this rapid trek through the life of a muscle, how the production of a mature functional muscle from its early inception is orchestrated will be outlined in exceedingly broad strokes so as to convey the wide range of processes that must be engaged in order to generate a functional muscle. Hopefully, enough information will be provided to encourage those interested to explore further.

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.

Endocrine Control of Spermatogenesis in Teleost Fish

1982 ◽  
Vol 39 (1) ◽  
pp. 65-79 ◽  
Author(s):  
R. Billard ◽  
A. Fostier ◽  
C. Weil ◽  
B. Breton
Keyword(s):  
Sperm Quality ◽  
Practical Implication ◽  
Continuous Production ◽  
Cell Types ◽  
Target Cells ◽  
Endocrine Control ◽  
Gonadotropin Secretion ◽  
Goldfish Carassius Auratus ◽  
The Central Nervous System ◽  
Testicular Size

Very different testicular structures and spermatogenetic patterns have been found in fish of the teleost group. Two types of structures may be identified: (i) a tubular type with no lumen (in cyprinodonts); the cysts migrate from the blind end to the vas efferens during the process of spermatogenesis; (ii) a lobular type having a central lumen receiving the spermatozoa released from cysts which remain stationary along the lobule during spermatogenesis. Different spermatogenetic patterns are distinguished in salmonids and cyprinids. In the latter (carp, Cyprinus carpio, and goldfish, Carassius auratus), some germ cell types (e.g. type B spermatogonia and spermatozoa) are present throughout the year, allowing nearly continuous production of good-quality sperm. Studies of their endocrine patterns suggest that the GTH involved is controlled by external (mainly temperature but also photoperiod) and gonadal factors. The GTH stimulates androgen production and eventually controls spermatogenesis and spermiation. In salmonids, the two major events of the testicular cycle, spermatogenesis and spermiation, are temporally separated by a stage of spermatozoal "maturation" during which the spermatozoa undergo physiological changes. Sperm quality declines during the period of spermiation. The initiation of a new spermatogenetic cycle seems possible only when the spermatozoa have been eliminated from the testis, either by the normal process of spermiation or by intratesticular resorption. This also illustrates the spatial independence of spermatogenesis and spermiation. The endocrine pattern of spermatogenesis in salmonids is similar to that in carp but seems different as regards spermiation. This spermiation process includes two steps, initiation and amplification, which require different GTH levels and steroid balance. Among the steroids, 11-ketotestosterone is the major androgen found in the plasma, but its superiority over other androgens in regard to spermiation remains to be demonstrated. Environmental factors (photoperiodic changes and temperature) may act directly on the central nervous system to control gonadotropin secretion. Temperature may also directly influence the gonad, somatic or germ cells, and steroid metabolism which acts either locally on the gonad or more centrally. The regulation of spermatogenesis in fish appears to be more subtle than previously believed. Major unknowns are whether there is a second GTH and, if so, its site of action; which steroids are directly involved in the control of spermatogenesis in the lobules, and which are the target cells; and which factors regulate testicular size and which pituitary GTH secretion. Finally, the poor yield of spermiation is intriguing and requires further study, considering its practical implication in fish-farming.Key words: spermatogenesis, teleosts, salmonids, cyprinids

scholarly journals Joint inference and alignment of genome structures enables characterization of compartment-independent reorganization across cell types

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Lila Rieber ◽  
Shaun Mahony
Keyword(s):  
K562 Cells ◽  
Cell Types ◽  
Data Sets ◽  
Cell Type ◽  
Histone Marks ◽  
Joint Inference ◽  
3D Localization ◽  
Topologically Associated Domains ◽  
Cell Type Specific

Abstract Background Comparisons of Hi–C data sets between cell types and conditions have revealed differences in topologically associated domains (TADs) and A/B compartmentalization, which are correlated with differences in gene regulation. However, previous comparisons have focused on known forms of 3D organization while potentially neglecting other functionally relevant differences. We aimed to create a method to quantify all locus-specific differences between two Hi–C data sets. Results We developed MultiMDS to jointly infer and align 3D chromosomal structures from two Hi–C data sets, thereby enabling a new way to comprehensively quantify relocalization of genomic loci between cell types. We demonstrate this approach by comparing Hi–C data across a variety of cell types. We consistently find relocalization of loci with minimal difference in A/B compartment score. For example, we identify compartment-independent relocalizations between GM12878 and K562 cells that involve loci displaying enhancer-associated histone marks in one cell type and polycomb-associated histone marks in the other. Conclusions MultiMDS is the first tool to identify all loci that relocalize between two Hi–C data sets. Our method can identify 3D localization differences that are correlated with cell-type-specific regulatory activities and which cannot be identified using other methods.

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