7,734 results match your criteria formation heterochromatin

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

View Article and Full-Text PDF

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

View Article and Full-Text PDF

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

View Article and Full-Text PDF

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

View Article and Full-Text PDF

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

View Article and Full-Text PDF

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

View Article and Full-Text PDF

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

View Article and Full-Text PDF

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

View Article and Full-Text PDF

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

View Article and Full-Text PDF

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

View Article and Full-Text PDF

A protocol for transposon insertion sequencing in to identify factors that maintain heterochromatin.

STAR Protoc 2021 Jun 23;2(2):100392. Epub 2021 Mar 23.

Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

Transposon insertion sequencing (TIS) is a highly effective method used with bacteria to identify genes important for growth in any condition of interest. Previously, we adapted this method to identify essential genes of the yeast . Here, we describe modifications used to identify genes necessary for the formation of centromeric heterochromatin. Read More

View Article and Full-Text PDF

HP1 drives de novo 3D genome reorganization in early Drosophila embryos.

Nature 2021 May 14;593(7858):289-293. Epub 2021 Apr 14.

Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.

Fundamental features of 3D genome organization are established de novo in the early embryo, including clustering of pericentromeric regions, the folding of chromosome arms and the segregation of chromosomes into active (A-) and inactive (B-) compartments. However, the molecular mechanisms that drive de novo organization remain unknown. Here, by combining chromosome conformation capture (Hi-C), chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq), 3D DNA fluorescence in situ hybridization (3D DNA FISH) and polymer simulations, we show that heterochromatin protein 1a (HP1a) is essential for de novo 3D genome organization during Drosophila early development. Read More

View Article and Full-Text PDF

A fungal sirtuin modulates development and virulence in the insect pathogen, Beauveria bassiana.

Environ Microbiol 2021 Apr 5. Epub 2021 Apr 5.

Department of Microbiology and Cell Science, University of Florida, Bldg. 981, Museum Rd, Gainesville, FL, 32611, USA.

Chromatin transitions are mediated in part by acetylation/deacetylation post-translational modifications of histones. Histone deacetylases, e.g. Read More

View Article and Full-Text PDF

Stress and odorant receptor feedback during a critical period after hatching regulates olfactory sensory neuron differentiation in Drosophila.

PLoS Biol 2021 Apr 1;19(4):e3001101. Epub 2021 Apr 1.

Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Here, we reveal that the regulation of Drosophila odorant receptor (OR) expression during the pupal stage is permissive and imprecise. We found that directly after hatching an OR feedback mechanism both directs and refines OR expression. We demonstrate that, as in mice, dLsd1 and Su(var)3-9 balance heterochromatin formation to direct OR expression. Read More

View Article and Full-Text PDF

Regulation of HP1 protein by phosphorylation during transcriptional repression and cell cycle.

J Biochem 2021 Mar 27. Epub 2021 Mar 27.

Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, JAPAN, Tel: 81-3-5316-3220.

HP1 (Heterochromatin Protein 1), a key factor for the formation of heterochromatin, binds to the methylated lysine 9 of histone H3 (H3K9me), and represses transcription. While the H3K9me mark and HP1 binding are thought to be faithfully propagated to daughter cells, the heterochromatin structure could be dynamically regulated during cell cycle. As evidenced by the well-known phenomenon called Position Effect Variegation (PEV), heterochromatin structure is dynamically and stochastically altered during developmental processes, and thus the expression of genes within or in the vicinity of heterochromatin could be affected by mutations in factors regulating DNA replication as well as by other epigenetic factors. Read More

View Article and Full-Text PDF

Fucoidan induces ROS-dependent epigenetic modulation in cervical cancer HeLa cell.

Int J Biol Macromol 2021 Mar 24;181:180-192. Epub 2021 Mar 24.

Biochemistry and Environmental Toxicology, Laboratory # 103, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address:

Fucoidan is a sulfated polysaccharide obtained from marine algae and known for various pharmacological activities. In this study, we investigated the effect of Fucoidan on cell viability, redox balance, cytoskeletal component F-actin, HDAC inhibition, autophagy, and senescence phenomenon in human cervical cancer HeLa cell line in comparison to positive control suberoylanilide hydroxamic acid by flow cytometry, fluorescence microscopy, and western blotting. Our observations revealed that Fucoidan exposure induces cytotoxicity in HeLa cells via ROS and mitochondrial superoxide generation and loss of ATP. Read More

View Article and Full-Text PDF

In vitro study of the trypanocidal activity of anilinophenanthrolines against Trypanosoma cruzi.

Parasitol Int 2021 Mar 23;83:102338. Epub 2021 Mar 23.

Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro - UFRJ, 21491-590 Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro - UFRJ, 21491-590 Rio de Janeiro, RJ, Brazil. Electronic address:

Chagas disease is present in Latin America, North America, Europe, and Asia, where between 6 and 7 million people are infected. This illness is transmitted mainly by the insect vector during blood feeding and by oral transmission. Chagas disease is treated with benznidazole and its effectiveness depends on which phase of the disease the treatment starts. Read More

View Article and Full-Text PDF

G-quadruplexes originating from evolutionary conserved L1 elements interfere with neuronal gene expression in Alzheimer's disease.

Nat Commun 2021 03 23;12(1):1828. Epub 2021 Mar 23.

Stem Cell and Developmental Biology Laboratory, Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada.

DNA sequences containing consecutive guanines organized in 4-interspaced tandem repeats can form stable single-stranded secondary structures, called G-quadruplexes (G4). Herein, we report that the Polycomb group protein BMI1 is enriched at heterochromatin regions containing putative G4 DNA sequences, and that G4 structures accumulate in cells with reduced BMI1 expression and/or relaxed chromatin, including sporadic Alzheimer's disease (AD) neurons. In AD neurons, G4 structures preferentially accumulate in lamina-associated domains, and this is rescued by re-establishing chromatin compaction. Read More

View Article and Full-Text PDF

Transcriptional regulation of telomeric repeat-containing RNA by acridine derivatives.

RNA Biol 2021 Mar 22:1-17. Epub 2021 Mar 22.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, Guangzhou and P.R. China.

Telomere is a specialized DNA-protein complex that plays an important role in maintaining chromosomal integrity. Shelterin is a protein complex formed by six different proteins, with telomeric repeat factors 1 (TRF1) and 2 (TRF2) binding to double-strand telomeric DNA. Telomeric DNA consists of complementary G-rich and C-rich repeats, which could form G-quadruplex and intercalated motif (i-motif), respectively, during cell cycle. Read More

View Article and Full-Text PDF

Targeting KDM4A epigenetically activates tumor-cell-intrinsic immunity by inducing DNA replication stress.

Mol Cell 2021 Mar 11. Epub 2021 Mar 11.

Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

Developing strategies to activate tumor-cell-intrinsic immune response is critical for improving tumor immunotherapy by exploiting tumor vulnerability. KDM4A, as a histone H3 lysine 9 trimethylation (H3K9me3) demethylase, has been found to play a critical role in squamous cell carcinoma (SCC) growth and metastasis. Here we report that KDM4A inhibition promoted heterochromatin compaction and induced DNA replication stress, which elicited antitumor immunity in SCC. Read More

View Article and Full-Text PDF

Nutrient-sensitive heterochromatization by TOR.

Ronit Weisman

Nat Cell Biol 2021 03;23(3):214-216

Department of Natural and Life Sciences, The Open University of Israel, Ra'anana, Israel.

View Article and Full-Text PDF

Schistosoma mansoni Heterochromatin Protein 1 (HP1) nuclear interactome in cercariae.

J Proteomics 2021 May 1;239:104170. Epub 2021 Mar 1.

Department of Animal Biology, Institute of Biology, University of Campinas, Campinas, Sao Paulo, Brazil. Electronic address:

Schistosoma mansoni causes schistosomiasis, which affects 240 million people, and 700 million people are living at risk of infection. Epigenetic mechanisms are important for transcriptional control and are well-known conserved transcriptional co-regulators in evolution, already described in mammal, yeast, protozoa and S. mansoni, responsible for heterochromatization and gene silence mechanisms through the formation of complexes of transcriptional repression in chromatin. Read More

View Article and Full-Text PDF

HP1β carries an acidic linker domain and requires H3K9me3 for phase separation.

Nucleus 2021 12;12(1):44-57

Center for Molecular Biosystems (BioSysM), Faculty of Biology, Ludwig-Maximilians-Universität München, Munich, Germany.

Liquid-liquid phase separation (LLPS) mediated formation of membraneless organelles has been proposed to coordinate biological processes in space and time. Previously, the formation of phase-separated droplets was described as a unique property of HP1α. Here, we demonstrate that the positive net charge of the intrinsically disordered hinge region (IDR-H) of HP1 proteins is critical for phase separation and that the exchange of four acidic amino acids is sufficient to confer LLPS properties to HP1β. Read More

View Article and Full-Text PDF
December 2021

Integrative pan cancer analysis reveals epigenomic variation in cancer type and cell specific chromatin domains.

Nat Commun 2021 03 3;12(1):1419. Epub 2021 Mar 3.

Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA.

Epigenetic mechanisms contribute to the initiation and development of cancer, and epigenetic variation promotes dynamic gene expression patterns that facilitate tumor evolution and adaptation. While the NCI-60 panel represents a diverse set of human cancer cell lines that has been used to screen chemical compounds, a comprehensive epigenomic atlas of these cells has been lacking. Here, we report an integrative analysis of 60 human cancer epigenomes, representing a catalog of activating and repressive histone modifications. Read More

View Article and Full-Text PDF

Shaggy functions downstream of dMyc and their concurrent downregulation confers additive rescue against tau toxicity in Drosophila.

Biofactors 2021 Mar 2. Epub 2021 Mar 2.

Department of Genetics, University of Delhi South Campus, New Delhi, India.

Neurodegenerative tauopathies such as Alzheimer's and Parkinson's diseases are characterized by hyperphosphorylation of tau protein and their subsequent aggregation in the forms of paired helical filaments and/or neurofibrillary tangles in specific areas of the brain. Despite several attempts, it remains a challenge to develop reliable biomarkers or effective drugs against tauopathies. It is increasingly evident now that due to the involvement of multiple cellular cascades affected by the pathogenic tau molecules, a single genetic modifier or a molecule is unlikely to be efficient enough to provide an inclusive rescue. Read More

View Article and Full-Text PDF

The function and regulation mechanism of piRNAs in human cancers.

Histol Histopathol 2021 Mar 2:18323. Epub 2021 Mar 2.

Department of Obstetrics and Gynecology, Center for Reproductive Medicine/Department of Fetal Medicine and Prenatal Diagnosis/BioResource Research Center, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Piwi-interacting RNAs (piRNAs) are mainly expressed in mammalian germ cells, playing an important role in maintaining germ line DNA integrity, inhibiting transposon transcription and translation, participating in heterochromatin formation, epigenetic regulation, and germ cell genesis. They combine with P-element induced wimpy testis (PIWI) proteins to form effector complexes known as piRNA-induced silencing complexes (pi-RISC) to regulate the gene silencing pathway. Recent evidence suggests that numerous piRNAs, with tumor-promoting and tumor-suppressing functions in cancer development, are dysregulated in tumor tissues, and are related to clinical prognosis. Read More

View Article and Full-Text PDF

Conserved dual-mode gene regulation programs in higher eukaryotes.

Nucleic Acids Res 2021 03;49(5):2583-2597

Davis Center for Regenerative Biology and Medicine, MDI Biological Laboratory, Bar Harbor, ME 04609, USA.

Recent genomic data analyses have revealed important underlying logics in eukaryotic gene regulation, such as CpG islands (CGIs)-dependent dual-mode gene regulation. In mammals, genes lacking CGIs at their promoters are generally regulated by interconversion between euchromatin and heterochromatin, while genes associated with CGIs constitutively remain as euchromatin. Whether a similar mode of gene regulation exists in non-mammalian species has been unknown. Read More

View Article and Full-Text PDF

Sir3 mediates long-range chromosome interactions in budding yeast.

Genome Res 2021 Mar 12;31(3):411-425. Epub 2021 Feb 12.

Institut Curie, PSL University, Sorbonne Université, CNRS, Nuclear Dynamics, 75005 Paris, France.

Physical contacts between distant loci contribute to regulate genome function. However, the molecular mechanisms responsible for settling and maintaining such interactions remain poorly understood. Here, we investigate the well-conserved interactions between heterochromatin loci. Read More

View Article and Full-Text PDF

TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell proliferation.

Nat Cell Biol 2021 03 11;23(3):243-256. Epub 2021 Feb 11.

Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Cell proliferation and differentiation require signalling pathways that enforce appropriate and timely gene expression. We find that Tor2, the catalytic subunit of the TORC1 complex in fission yeast, targets a conserved nuclear RNA elimination network, particularly the serine and proline-rich protein Pir1, to control gene expression through RNA decay and facultative heterochromatin assembly. Phosphorylation by Tor2 protects Pir1 from degradation by the ubiquitin-proteasome system involving the polyubiquitin Ubi4 stress-response protein and the Cul4-Ddb1 E3 ligase. Read More

View Article and Full-Text PDF

Molecular principles of Piwi-mediated cotranscriptional silencing through the dimeric SFiNX complex.

Genes Dev 2021 Mar 11;35(5-6):392-409. Epub 2021 Feb 11.

Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria.

Nuclear Argonaute proteins, guided by their bound small RNAs to nascent target transcripts, mediate cotranscriptional silencing of transposons and repetitive genomic loci through heterochromatin formation. The molecular mechanisms involved in this process are incompletely understood. Here, we show that the SFiNX complex, a silencing mediator downstream from nuclear Piwi-piRNA complexes in , facilitates cotranscriptional silencing as a homodimer. Read More

View Article and Full-Text PDF