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Epigenomes, Volume 5, Issue 4 (December 2021) – 7 articles

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Article
The Histone H3 K4me3, K27me3, and K27ac Genome-Wide Distributions Are Differently Influenced by Sex in Brain Cortexes and Gastrocnemius of the Alzheimer’s Disease PSAPP Mouse Model
Epigenomes 2021, 5(4), 26; https://doi.org/10.3390/epigenomes5040026 - 25 Nov 2021
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Abstract
Background: Women represent the majority of Alzheimer’s disease patients and show typical symptoms. Genetic, hormonal, and behavioral mechanisms have been proposed to explain sex differences in dementia prevalence. However, whether sex differences exist in the epigenetic landscape of neuronal tissue during the progression [...] Read more.
Background: Women represent the majority of Alzheimer’s disease patients and show typical symptoms. Genetic, hormonal, and behavioral mechanisms have been proposed to explain sex differences in dementia prevalence. However, whether sex differences exist in the epigenetic landscape of neuronal tissue during the progression of the disease is still unknown. Methods: To investigate the differences of histone H3 modifications involved in transcription, we determined the genome-wide profiles of H3K4me3, H3K27ac, and H3K27me3 in brain cortexes of an Alzheimer mouse model (PSAPP). Gastrocnemius muscles were also tested since they are known to be different in the two sexes and are affected during the disease progression. Results: Correlation analysis distinguished the samples based on sex for H3K4me3 and H3K27me3 but not for H3K27ac. The analysis of transcription starting sites (TSS) signal distribution, and analysis of bounding sites revealed that gastrocnemius is more influenced than brain by sex for the three histone modifications considered, exception made for H3K27me3 distribution on the X chromosome which showed sex-related differences in promoters belonging to behavior and cellular or neuronal spheres in mice cortexes. Conclusions: H3K4me3, H3K27ac, and H3K27me3 signals are slightly affected by sex in brain, with the exception of H3K27me3, while a higher number of differences can be found in gastrocnemius. Full article
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Review
Epigenetic Modifications in Plant Development and Reproduction
Epigenomes 2021, 5(4), 25; https://doi.org/10.3390/epigenomes5040025 - 19 Nov 2021
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Abstract
Plants are exposed to highly fluctuating effects of light, temperature, weather conditions, and many other environmental factors throughout their life. As sessile organisms, unlike animals, they are unable to escape, hide, or even change their position. Therefore, the growth and development of plants [...] Read more.
Plants are exposed to highly fluctuating effects of light, temperature, weather conditions, and many other environmental factors throughout their life. As sessile organisms, unlike animals, they are unable to escape, hide, or even change their position. Therefore, the growth and development of plants are largely determined by interaction with the external environment. The success of this interaction depends on the ability of the phenotype plasticity, which is largely determined by epigenetic regulation. In addition to how environmental factors can change the patterns of genes expression, epigenetic regulation determines how genetic expression changes during the differentiation of one cell type into another and how patterns of gene expression are passed from one cell to its descendants. Thus, one genome can generate many ‘epigenomes’. Epigenetic modifications acquire special significance during the formation of gametes and plant reproduction when epigenetic marks are eliminated during meiosis and early embryogenesis and later reappear. However, during asexual plant reproduction, when meiosis is absent or suspended, epigenetic modifications that have arisen in the parental sporophyte can be transmitted to the next clonal generation practically unchanged. In plants that reproduce sexually and asexually, epigenetic variability has different adaptive significance. In asexuals, epigenetic regulation is of particular importance for imparting plasticity to the phenotype when, apart from mutations, the genotype remains unchanged for many generations of individuals. Of particular interest is the question of the possibility of transferring acquired epigenetic memory to future generations and its potential role for natural selection and evolution. All these issues will be discussed to some extent in this review. Full article
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Review
The Regulation of Plant Vegetative Phase Transition and Rejuvenation: miRNAs, a Key Regulator
Epigenomes 2021, 5(4), 24; https://doi.org/10.3390/epigenomes5040024 - 18 Oct 2021
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Abstract
In contrast to animals, adult organs in plants are not formed during embryogenesis but generated from meristematic cells as plants advance through development. Plant development involves a succession of different phenotypic stages and the transition between these stages is termed phase transition. Phase [...] Read more.
In contrast to animals, adult organs in plants are not formed during embryogenesis but generated from meristematic cells as plants advance through development. Plant development involves a succession of different phenotypic stages and the transition between these stages is termed phase transition. Phase transitions need to be tightly regulated and coordinated to ensure they occur under optimal seasonal, environmental conditions. Polycarpic perennials transition through vegetative stages and the mature, reproductive stage many times during their lifecycles and, in both perennial and annual species, environmental factors and culturing methods can reverse the otherwise unidirectional vector of plant development. Epigenetic factors regulating gene expression in response to internal cues and external (environmental) stimuli influencing the plant’s phenotype and development have been shown to control phase transitions. How developmental and environmental cues interact to epigenetically alter gene expression and influence these transitions is not well understood, and understanding this interaction is important considering the current climate change scenarios, since epigenetic maladaptation could have catastrophic consequences for perennial plants in natural and agricultural ecosystems. Here, we review studies focusing on the epigenetic regulators of the vegetative phase change and highlight how these mechanisms might act in exogenously induced plant rejuvenation and regrowth following stress. Full article
(This article belongs to the Special Issue Mechanisms of Plant Epigenome Dynamics)
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Review
G9a: An Emerging Epigenetic Target for Melanoma Therapy
Epigenomes 2021, 5(4), 23; https://doi.org/10.3390/epigenomes5040023 - 12 Oct 2021
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Abstract
Epigenetic regulation is a crucial component of DNA maintenance and cellular identity. As our understanding of the vast array of proteins that contribute to chromatin accessibility has advanced, the role of epigenetic remodelers in disease has become more apparent. G9a is a histone [...] Read more.
Epigenetic regulation is a crucial component of DNA maintenance and cellular identity. As our understanding of the vast array of proteins that contribute to chromatin accessibility has advanced, the role of epigenetic remodelers in disease has become more apparent. G9a is a histone methyltransferase that contributes to immune cell differentiation and function, neuronal development, and has been implicated in diseases, including cancer. In melanoma, recurrent mutations and amplifications of G9a have led to its identification as a therapeutic target. The pathways that are regulated by G9a provide an insight into relevant biomarkers for patient stratification. Future work is aided by the breadth of literature on G9a function during normal differentiation and development, along with similarities to EZH2, another histone methyltransferase that forms a synthetic lethal relationship with members of the SWI/SNF complex in certain cancers. Here, we review the literature on G9a, its role in melanoma, and lessons from EZH2 inhibitor studies. Full article
(This article belongs to the Special Issue Epigenetics of Melanoma)
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Review
One Omics Approach Does Not Rule Them All: The Metabolome and the Epigenome Join Forces in Haematological Malignancies
Epigenomes 2021, 5(4), 22; https://doi.org/10.3390/epigenomes5040022 - 08 Oct 2021
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Abstract
Aberrant DNA methylation, dysregulation of chromatin-modifying enzymes, and microRNAs (miRNAs) play a crucial role in haematological malignancies. These epimutations, with an impact on chromatin accessibility and transcriptional output, are often associated with genomic instability and the emergence of drug resistance, disease progression, and [...] Read more.
Aberrant DNA methylation, dysregulation of chromatin-modifying enzymes, and microRNAs (miRNAs) play a crucial role in haematological malignancies. These epimutations, with an impact on chromatin accessibility and transcriptional output, are often associated with genomic instability and the emergence of drug resistance, disease progression, and poor survival. In order to exert their functions, epigenetic enzymes utilize cellular metabolites as co-factors and are highly dependent on their availability. By affecting the expression of metabolic enzymes, epigenetic modifiers may aid the generation of metabolite signatures that could be utilized as targets and biomarkers in cancer. This interdependency remains often neglected and poorly represented in studies, despite well-established methods to study the cellular metabolome. This review critically summarizes the current knowledge in the field to provide an integral picture of the interplay between epigenomic alterations and the cellular metabolome in haematological malignancies. Our recent findings defining a distinct metabolic signature upon response to enhancer of zeste homolog 2 (EZH2) inhibition in multiple myeloma (MM) highlight how a shift of preferred metabolic pathways may potentiate novel treatments. The suggested link between the epigenome and the metabolome in haematopoietic tumours holds promise for the use of metabolic signatures as possible biomarkers of response to treatment. Full article
(This article belongs to the Special Issue Epigenetic Cancer Therapy: Targeting DNA and Histone Methylation)
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Review
Role of Enhancers in Development and Diseases
Epigenomes 2021, 5(4), 21; https://doi.org/10.3390/epigenomes5040021 - 04 Oct 2021
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Abstract
Enhancers are cis-regulatory elements containing short DNA sequences that serve as binding sites for pioneer/regulatory transcription factors, thus orchestrating the regulation of genes critical for lineage determination. The activity of enhancer elements is believed to be determined by transcription factor binding, thus determining [...] Read more.
Enhancers are cis-regulatory elements containing short DNA sequences that serve as binding sites for pioneer/regulatory transcription factors, thus orchestrating the regulation of genes critical for lineage determination. The activity of enhancer elements is believed to be determined by transcription factor binding, thus determining the cell state identity during development. Precise spatio-temporal control of the transcriptome during lineage specification requires the coordinated binding of lineage-specific transcription factors to enhancers. Thus, enhancers are the primary determinants of cell identity. Numerous studies have explored the role and mechanism of enhancers during development and disease, and various basic questions related to the functions and mechanisms of enhancers have not yet been fully answered. In this review, we discuss the recently published literature regarding the roles of enhancers, which are critical for various biological processes governing development. Furthermore, we also highlight that altered enhancer landscapes provide an essential context to understand the etiologies and mechanisms behind numerous complex human diseases, providing new avenues for effective enhancer-based therapeutic interventions. Full article
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Review
Clinical Utility of Epigenetic Changes in Pancreatic Adenocarcinoma
Epigenomes 2021, 5(4), 20; https://doi.org/10.3390/epigenomes5040020 - 27 Sep 2021
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Abstract
Pancreatic cancer is a molecularly heterogeneous disease. Epigenetic changes and epigenetic regulatory mechanisms underlie at least some of this heterogeneity and contribute to the evolution of aggressive tumor biology in patients and the tumor’s intrinsic resistance to therapy. Here we review our current [...] Read more.
Pancreatic cancer is a molecularly heterogeneous disease. Epigenetic changes and epigenetic regulatory mechanisms underlie at least some of this heterogeneity and contribute to the evolution of aggressive tumor biology in patients and the tumor’s intrinsic resistance to therapy. Here we review our current understanding of epigenetic dysregulation in pancreatic cancer and how it is contributing to our efforts in early diagnosis, predictive and prognostic biomarker development and new therapeutic approaches in this deadly cancer. Full article
(This article belongs to the Special Issue Epigenetics of Pancreatic Cancer 2.0)
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