16,382 results match your criteria heterochromatin


Enhanced targeted DNA methylation with dCas9-DNMT3A3L of the CMV and endogenous promoters entails distinct subsequent histone modification changes in CHO cells.

Metab Eng 2021 May 6. Epub 2021 May 6.

BOKU University of Natural Resources and Life Sciences, Vienna, Austria; Austrian Center for Industrial Biotechnology GmbH, Vienna, Austria. Electronic address:

With the emergence of new CRISPR/dCas9 tools that enable site specific modulation of DNA methylation and histone modifications, more detailed investigations of the contribution of epigenetic regulation to the precise phenotype of cells in culture, including recombinant production subclones, is now possible. These also allow a wide range of applications in metabolic engineering once the impact of such epigenetic modifications on the chromatin state is available. In this study, enhanced DNA methylation tools were targeted to a recombinant viral promoter (CMV), an endogenous promoter that is silenced in its native state in CHO cells, but had been reactivated previously (β-galactoside α-2,6-sialyltransferase 1) and an active endogenous promoter (α-1,6-fucosyltransferase), respectively. Read More

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Purifying selection on noncoding deletions of human regulatory loci detected using their cellular pleiotropy.

Genome Res 2021 May 7. Epub 2021 May 7.

Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.

Genomic deletions provide a powerful loss-of-function model in noncoding regions to assess the role of purifying selection on genetic variation. Regulatory element function is characterized by nonuniform tissue and cell type activity, necessarily linking the study of fitness consequences from regulatory variants to their corresponding cellular activity. We generated a callset of deletions from genomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) and used deletions from The 1000 Genomes Project Consortium (1000GP) in order to examine whether purifying selection preserves noncoding sites of chromatin accessibility marked by DNase I hypersensitivity (DHS), histone modification (enhancer, transcribed, Polycomb-repressed, heterochromatin), and chromatin loop anchors. Read More

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Loss of EZH2-like or SU(VAR)3-9-like proteins causes simultaneous perturbations in H3K27 and H3K9 tri-methylation and associated developmental defects in the fungus Podospora anserina.

Epigenetics Chromatin 2021 May 7;14(1):22. Epub 2021 May 7.

Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, 91198, Gif-sur-Yvette, France.

Background: Selective gene silencing is key to development. It is generally accepted that H3K27me3-enriched heterochromatin maintains transcriptional repression established during early development and regulates cell fate. Conversely, H3K9me3-enriched heterochromatin prevents differentiation but constitutes protection against transposable elements. Read More

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Embryo CHH hypermethylation is mediated by RdDM and is autonomously directed in Brassica rapa.

Genome Biol 2021 May 6;22(1):140. Epub 2021 May 6.

The School of Plant Sciences, The University of Arizona, Tucson, AZ, 85721, USA.

Background: RNA-directed DNA methylation (RdDM) initiates cytosine methylation in all contexts and maintains asymmetric CHH methylation. Mature plant embryos show one of the highest levels of CHH methylation, and it has been suggested that RdDM is responsible for this hypermethylation. Because loss of RdDM in Brassica rapa causes seed abortion, embryo methylation might play a role in seed development. Read More

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An Arabidopsis AT-hook motif nuclear protein mediates somatic embryogenesis and coinciding genome duplication.

Nat Commun 2021 05 4;12(1):2508. Epub 2021 May 4.

Plant Developmental Genetics, Institute of Biology Leiden, Leiden University, Leiden, Netherlands.

Plant somatic cells can be reprogrammed into totipotent embryonic cells that are able to form differentiated embryos in a process called somatic embryogenesis (SE), by hormone treatment or through overexpression of certain transcription factor genes, such as BABY BOOM (BBM). Here we show that overexpression of the AT-HOOK MOTIF CONTAINING NUCLEAR LOCALIZED 15 (AHL15) gene induces formation of somatic embryos on Arabidopsis thaliana seedlings in the absence of hormone treatment. During zygotic embryogenesis, AHL15 expression starts early in embryo development, and AH15 and other AHL genes are required for proper embryo patterning and development beyond the globular stage. Read More

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FVE promotes RNA-directed DNA methylation by facilitating the association of RNA polymerase V with chromatin.

Plant J 2021 May 3. Epub 2021 May 3.

National Institute of Biological Sciences, Beijing, 102206, China.

Association of RNA polymerase V (Pol V) with chromatin is a critical step for RNA- directed DNA methylation (RdDM) in plants. Although the methylated-DNA-binding proteins SUVH2 and SUVH9 and the chromatin-remodeler-containing complex DDR are known to be required for the association of Pol V with chromatin, the molecular mechanisms underlying the association of Pol V with different chromatin environments remain largely unknown. Here we found that SUVH9 interacts with FVE, a homologue of the mammalian retinoblastoma-associated protein, which has been previously identified as a shared subunit of the histone deacetylase complex and the polycomb-type histone H3K27 trimethyltransferase complex. Read More

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DNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation.

Nat Commun 2021 05 3;12(1):2490. Epub 2021 May 3.

Department of Biochemistry, University of California, Riverside, CA, USA.

DNA methylation and trimethylated histone H4 Lysine 20 (H4K20me3) constitute two important heterochromatin-enriched marks that frequently cooperate in silencing repetitive elements of the mammalian genome. However, it remains elusive how these two chromatin modifications crosstalk. Here, we report that DNA methyltransferase 1 (DNMT1) specifically 'recognizes' H4K20me3 via its first bromo-adjacent-homology domain (DNMT1). Read More

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Autism-associated vigilin depletion impairs DNA damage repair.

Mol Cell Biol 2021 May 3. Epub 2021 May 3.

Chromatin and Epigenetics Lab, Department of Biotechnology, University of Kashmir, Srinagar, Jammu and Kashmir 190006, India.

Vigilin (Vgl1) is essential for heterochromatin formation, chromosome segregation, mRNA stability and is associated with autism-spectrum disorders and cancer, vigilin, for example, can suppress proto-oncogene c-fms expression in breast cancer. Conserved from yeast to humans, vigilin is an RNA-binding protein with 14 tandemly arranged nonidentical hnRNP K type homology (KH) domains. Here we report that vigilin depletion increased cell sensitivity to cisplatin- or ionizing radiation (IR)-induced cell death and genomic instability due to defective DNA repair. Read More

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Three putative DNA methyltransferases of Verticillium dahliae differentially contribute to DNA methylation that is dispensable for growth, development and virulence.

Epigenetics Chromatin 2021 May 3;14(1):21. Epub 2021 May 3.

Laboratory of Phytopathology, Wageningen University and Research, Droevendaalsesteeg 1, 6708 PB, Wageningen, The Netherlands.

Background: DNA methylation is an important epigenetic control mechanism that in many fungi is restricted to genomic regions containing transposable elements (TEs). Two DNA methyltransferases, Dim2 and Dnmt5, are known to perform methylation at cytosines in fungi. While most ascomycete fungi encode both Dim2 and Dnmt5, only few functional studies have been performed in species containing both. Read More

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Mitochondrial cytochrome c shot towards histone chaperone condensates in the nucleus.

FEBS Open Bio 2021 May 3. Epub 2021 May 3.

Institute for Chemical Research (IIQ), Scientific Research Centre Isla de la Cartuja (cicCartuja), University of Seville - CSIC, Avda. Américo Vespucio 49, Sevilla, 41092, Spain.

Despite mitochondria being key for the control of cell homeostasis and fate, their role in DNA damage response (DDR) is usually just regarded as an apoptotic trigger. However, growing evidence points to mitochondrial factors modulating nuclear functions. Remarkably, after DNA damage, cytochrome c (Cc) interacts in the cell nucleus with a variety of well-known histone chaperones, whose activity is competitively inhibited by the hemeprotein. Read More

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Heterochromatin and Polycomb as regulators of haematopoiesis.

Biochem Soc Trans 2021 Apr 30. Epub 2021 Apr 30.

The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria3052, Australia.

Haematopoiesis is the process by which multipotent haematopoietic stem cells are transformed into each and every type of terminally differentiated blood cell. Epigenetic silencing is critical for this process by regulating the transcription of cell-cycle genes critical for self-renewal and differentiation, as well as restricting alternative fate genes to allow lineage commitment and appropriate differentiation. There are two distinct forms of transcriptionally repressed chromatin: H3K9me3-marked heterochromatin and H3K27me3/H2AK119ub1-marked Polycomb (often referred to as facultative heterochromatin). Read More

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Cytogenetic Analysis, Heterochromatin Characterization and Location of the rDNA Genes of (Coleoptera, Meloidae); A Species with an Unexpected High Number of rDNA Clusters.

Insects 2021 Apr 26;12(5). Epub 2021 Apr 26.

Department of Experimental Biology, Genetics Area, University of Jaén, 23071 Jaén, Spain.

Meloidae are commonly known as blister beetles, so called for the secretion of cantharidin, a toxic substance that causes irritation and blistering. There has been a recent increase in the interest of the cantharidin anticancer potential of this insect group. Cytogenetic and molecular data in this group are scarce. Read More

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Hydroxyurea and Caffeine Impact pRb-like Protein-Dependent Chromatin Architecture Profiles in Interphase Cells of .

Int J Mol Sci 2021 Apr 27;22(9). Epub 2021 Apr 27.

Department of Cytophysiology, Institute of Experimental Biology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.

The survival of cells depends on their ability to replicate correctly genetic material. Cells exposed to replication stress can experience a number of problems that may lead to deregulated proliferation, the development of cancer, and/or programmed cell death. In this article, we have induced prolonged replication arrest via hydroxyurea (HU) treatment and also premature chromosome condensation (PCC) by co-treatment with HU and caffeine (CF) in the root meristem cells of . Read More

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Sequence, Chromatin and Evolution of Satellite DNA.

Int J Mol Sci 2021 Apr 21;22(9). Epub 2021 Apr 21.

Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Satellite DNA consists of abundant tandem repeats that play important roles in cellular processes, including chromosome segregation, genome organization and chromosome end protection. Most satellite DNA repeat units are either of nucleosomal length or 5-10 bp long and occupy centromeric, pericentromeric or telomeric regions. Due to high repetitiveness, satellite DNA sequences have largely been absent from genome assemblies. Read More

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Interplay between Histone and DNA Methylation Seen through Comparative Methylomes in Rare Mendelian Disorders.

Int J Mol Sci 2021 Apr 3;22(7). Epub 2021 Apr 3.

Université de Paris, Epigenetics and Cell Fate, CNRS UMR7216, 75013 Paris, France.

DNA methylation (DNAme) profiling is used to establish specific biomarkers to improve the diagnosis of patients with inherited neurodevelopmental disorders and to guide mutation screening. In the specific case of mendelian disorders of the epigenetic machinery, it also provides the basis to infer mechanistic aspects with regard to DNAme determinants and interplay between histone and DNAme that apply to humans. Here, we present comparative methylomes from patients with mutations in the de novo DNA methyltransferases DNMT3A and DNMT3B, in their catalytic domain or their N-terminal parts involved in reading histone methylation, or in histone H3 lysine (K) methylases NSD1 or SETD2 (H3 K36) or KMT2D/MLL2 (H3 K4). Read More

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Chromatin Regulator SPEN/SHARP in X Inactivation and Disease.

Cancers (Basel) 2021 Apr 1;13(7). Epub 2021 Apr 1.

Institute of Biochemistry, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany.

Enzymes, such as histone methyltransferases and demethylases, histone acetyltransferases and deacetylases, and DNA methyltransferases are known as epigenetic modifiers that are often implicated in tumorigenesis and disease. One of the best-studied chromatin-based mechanism is X chromosome inactivation (XCI), a process that establishes facultative heterochromatin on only one X chromosome in females and establishes the right dosage of gene expression. The specificity factor for this process is the long non-coding RNA (), which is upregulated from one X chromosome in female cells. Read More

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PRSS50 is a testis protease responsible for proper sperm tail formation and function.

Development 2021 Apr 16;148(8). Epub 2021 Apr 16.

Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030, USA.

Multiple morphological abnormalities of the sperm flagella (MMAF) are a major cause of asthenoteratozoospermia. We have identified protease serine 50 (PRSS50) as having a crucial role in sperm development, because Prss50-null mice presented with impaired fertility and sperm tail abnormalities. PRSS50 could also be involved in centrosome function because these mice showed a threefold increase in acephalic sperm (head-tail junction defect), sperm with multiple heads (spermatid division defect) and sperm with multiple tails, including novel two conjoined sperm (complete or partial parts of several flagellum on the same plasma membrane). Read More

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The role of nuclear Ca2+ in maintaining neuronal homeostasis and brain health.

J Cell Sci 2021 Apr 22;134(8). Epub 2021 Apr 22.

Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.

Nuclear Ca2+ has emerged as one of the most potent mediators of the dialogue between neuronal synapses and the nucleus that regulates heterochromatin states, transcription factor activity, nuclear morphology and neuronal gene expression induced by synaptic activity. Recent studies underline the importance of nuclear Ca2+ signaling in long-lasting, activity-induced adaptation and maintenance of proper brain function. Diverse forms of neuroadaptation require transient nuclear Ca2+ signaling and cyclic AMP-responsive element-binding protein (CREB1, referred to here as CREB) as its prime target, which works as a tunable switch to drive and modulate specific gene expression profiles associated with memory, pain, addiction and neuroprotection. Read More

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Ameliorative effects of colostrum against DMBA hepatotoxicity in rats.

Saudi J Biol Sci 2021 Apr 23;28(4):2254-2266. Epub 2021 Jan 23.

Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.

Colostrum, the sole diet for newborns, is an emerging nutraceutical. To date, the chemopreventive effect of Bovine Colostrum against liver injury induced by the potent carcinogen, 7,12-dimethyl-Benz[a]anthracene (DMBA) is unexplored. Humans are daily exposed to DMBA which is a highly lipophilic environmental organic pollutant. Read More

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ATRX limits the accessibility of histone H3-occupied HSV genomes during lytic infection.

PLoS Pathog 2021 Apr 28;17(4):e1009567. Epub 2021 Apr 28.

Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, United States of America.

Histones are rapidly loaded on the HSV genome upon entry into the nucleus of human fibroblasts, but the effects of histone loading on viral replication have not been fully defined. We showed recently that ATRX is dispensable for de novo deposition of H3 to HSV genomes after nuclear entry but restricted infection through maintenance of viral heterochromatin. To further investigate the roles that ATRX and other histone H3 chaperones play in restriction of HSV, we infected human fibroblasts that were systematically depleted of nuclear H3 chaperones. Read More

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Potential Functions of Histone H3.3 Lysine 56 Acetylation in Mammals.

Epigenetics 2021 Apr 26. Epub 2021 Apr 26.

Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, USA.

H3K56 acetylation (H3K56Ac) was first identified in yeast and has recently been reported to play important roles in maintaining genomic stability, chromatin assembly, DNA replication, cell cycle progression and DNA repair. Although H3.1K56Ac has been relatively well studied, the function of H3. Read More

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Imaging the response to DNA damage in heterochromatin domains reveals core principles of heterochromatin maintenance.

Nat Commun 2021 04 23;12(1):2428. Epub 2021 Apr 23.

Epigenetics and Cell Fate Centre, UMR7216 CNRS, Université de Paris, Paris, France.

Heterochromatin is a critical chromatin compartment, whose integrity governs genome stability and cell fate transitions. How heterochromatin features, including higher-order chromatin folding and histone modifications associated with transcriptional silencing, are maintained following a genotoxic stress challenge is unknown. Here, we establish a system for targeting UV damage to pericentric heterochromatin in mammalian cells and for tracking the heterochromatin response to UV in real time. Read More

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Key changes in chromatin mark mammalian epidermal differentiation and ageing.

Epigenetics 2021 Apr 23:1-16. Epub 2021 Apr 23.

Epithelial Epigenetics and Development Laboratory, Skin Research Institute of Singapore, Singapore.

Dynamic shifts in chromatin states occur during embryonic epidermal development to support diverse epigenetic pathways that regulate skin formation and differentiation. However, it is not known whether the epigenomes established during embryonic development are maintained into adulthood or how these epigenetic mechanisms may be altered upon physiological ageing of the tissue. Here, we systematically profiled the nuclear enrichment of five key histone modifications in young and aged mouse epidermis and identified distinct chromatin states that are tightly correlated with cellular differentiation, as well as chromatin alterations that accompanied epidermal ageing. Read More

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Replication timing maintains the global epigenetic state in human cells.

Science 2021 04 22;372(6540):371-378. Epub 2021 Apr 22.

Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.

The temporal order of DNA replication [replication timing (RT)] is correlated with chromatin modifications and three-dimensional genome architecture; however, causal links have not been established, largely because of an inability to manipulate the global RT program. We show that loss of RIF1 causes near-complete elimination of the RT program by increasing heterogeneity between individual cells. RT changes are coupled with widespread alterations in chromatin modifications and genome compartmentalization. Read More

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Comparative Cytogenetics in Four Leptodactylus Species (Amphibia, Anura, Leptodactylidae): Evidence of Inner Chromosomal Diversification in Highly Conserved Karyotypes.

Cytogenet Genome Res 2021 Apr 22:1-11. Epub 2021 Apr 22.

Laboratório de Biologia Molecular, Evolução e Microbiologia, Instituto Federal do Pará, Abaetetuba, Brazil.

With 82 species currently described, the genus Leptodactylus is the most diverse and representative one in the family Leptodactylidae. Concerning chromosomal organization, this genus represents an interesting and underexplored group since data from molecular cytogenetics are incipient, and little is known about the organization and distribution of repetitive DNA elements in the karyotypes. In this sense, this study aimed at providing a comparative analysis in 4 Leptodactylus species (L. Read More

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Toxic Y chromosome: Increased repeat expression and age-associated heterochromatin loss in male Drosophila with a young Y chromosome.

PLoS Genet 2021 Apr 22;17(4):e1009438. Epub 2021 Apr 22.

Department of Integrative Biology, University of California Berkeley, Berkeley, California, United States of America.

Sex-specific differences in lifespan are prevalent across the tree of life and influenced by heteromorphic sex chromosomes. In species with XY sex chromosomes, females often outlive males. Males and females can differ in their overall repeat content due to the repetitive Y chromosome, and repeats on the Y might lower survival of the heterogametic sex (toxic Y effect). Read More

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Identification and characterization of repetitive DNA in the genus Didelphis Linnaeus, 1758 (Didelphimorphia, Didelphidae) and the use of satellite DNAs as phylogenetic markers.

Genet Mol Biol 2021 16;44(2):e20200384. Epub 2021 Apr 16.

Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Laboratório de Evolução de Mamíferos, Belo Horizonte, MG, Brazil.

Didelphis species have been shown to exhibit very conservative karyotypes, which mainly differ in their constitutive heterochromatin, known to be mostly composed by repetitive DNAs. In this study, we used genome skimming data combined with computational pipelines to identify the most abundant repetitive DNA families of Lutreolina crassicaudata and all six Didelphis species. We found that transposable elements (TEs), particularly LINE-1, endogenous retroviruses, and SINEs, are the most abundant mobile elements in the studied species. Read More

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Comparative cytogenetics of two species of (Chiroptera, Phyllostomidae) in Midwestern Brazil.

Comp Cytogenet 2021 2;15(2):89-99. Epub 2021 Apr 2.

Faculdade de Ciências Agrárias, Biológicas e Sociais Aplicadas, Universidade do Estado de Mato Grosso, Av. Prof. Dr. Renato Figueiro Varella, s/n, Nova Xavantina, MT, Brazil Universidade Federal do Mato Grosso Cuiabá Brazil.

Gervais, 1856 is represented by small frugivorous bats of the Stenodermatinae subfamily. The taxonomy of this group presents controversies and has been subject to changes, especially since the morphological characters evaluated have left gaps that are difficult to fill regarding good species characterization. Previous studies performed in Gervais, 1856 found that the karyotype of this species has a diploid number of chromosomes equal to 30 and 56 autosomal arms. Read More

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Epigenetics drive the evolution of sex chromosomes in animals and plants.

Philos Trans R Soc Lond B Biol Sci 2021 Jun 19;376(1826):20200124. Epub 2021 Apr 19.

The Francis Crick institute, London, UK.

We review how epigenetics affect sex chromosome evolution in animals and plants. In a few species, sex is determined epigenetically through the action of Y-encoded small RNAs. Epigenetics is also responsible for changing the sex of individuals through time, even in species that carry sex chromosomes, and could favour species adaptation through breeding system plasticity. Read More

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