5,096 results match your criteria epigenetic regulators

Oncogenic truncations of ASXL1 enhance a motif for BRD4 ET-domain binding.

J Mol Biol 2021 Sep 15:167242. Epub 2021 Sep 15.

Biochemistry Department, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand.

Proper regulation of gene-expression relies on specific protein-protein interactions between a myriad of epigenetic regulators. As such, mutation of genes encoding epigenetic regulators often drive cancer and developmental disorders. Additional sex combs-like protein 1 (ASXL1) is a key example, where mutations frequently drive haematological cancers and can cause developmental disorders. Read More

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September 2021

Identifying transcript 5' capped ends in .

PeerJ 2021 25;9:e11983. Epub 2021 Aug 25.

National Biobank of Thailand (NBT), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand.

Background: The genome of the human malaria parasite is poorly annotated, in particular, the 5' capped ends of its mRNA transcripts. New approaches are needed to fully catalog transcripts for understanding gene function and regulation in this organism.

Methods: We developed a transcriptomic method based on next-generation sequencing of complementary DNA (cDNA) enriched for full-length fragments using eIF4E, a 5' cap-binding protein, and an unenriched control. Read More

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Emerging roles of Bromodomain protein 4 in regulation of stem cell identity.

Stem Cells 2021 Sep 14. Epub 2021 Sep 14.

Molecular Biology Division, Bhabha Atomic Research Centre, Mumbai.

Understanding the mechanism of fate decision and lineage commitment is the key step for developing novel stem cell applications in therapeutics. This process is coordinately regulated through systematic epigenetic reprogramming and concomitant changes in the transcriptional landscape of the stem cells. One of the Bromo- and Extra-Terminal domain (BET) family member proteins, BRD4, performs the role of epigenetic reader and modulates gene expression by recruiting other transcription factors and directly regulating RNA polymerase II elongation. Read More

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September 2021

Histone Deacetylase as a Valuable Predictive Biomarker and Therapeutic Target in Immunotherapy for Non-Small Cell Lung Cancer.

Cancer Res Treat 2021 Sep 10. Epub 2021 Sep 10.

Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea.

Purpose: Histone deacetylase inhibitors (HDACis) are epigenetic regulators and used clinically for hematopoietic malignancies. Recently, HDACis have received attention as a factor that modulates the immune system. In this study, the role of HDAC expression as a predictive marker in lung cancer patients who were treated with immune checkpoint inhibitors (ICIs) and the role of HDACi and ICI combination treatment in the mouse tumor model were analyzed. Read More

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September 2021

Microbiome in drug resistance to colon cancer.

Curr Opin Physiol 2021 Oct 17;23. Epub 2021 Aug 17.

Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66160, USA.

Metagenomic analyses have revealed microbial dysbiosis in the gut of patients with colorectal cancer (CRC). The gut microbiota influences CRC via a variety of mechanisms, including microbial-derived factors such as metabolites or genotoxins. Pathogenic drivers and opportunistic passenger bacteria may underlie direct effect of the gut microbiota on carcinogenesis. Read More

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October 2021

Epigenetic Regulation of the Vascular Endothelium by Angiogenic LncRNAs.

Front Genet 2021 26;12:668313. Epub 2021 Aug 26.

Marsden Lab, Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.

The functional properties of the vascular endothelium are diverse and heterogeneous between vascular beds. This is especially evident when new blood vessels develop from a pre-existing closed cardiovascular system, a process termed angiogenesis. Endothelial cells are key drivers of angiogenesis as they undergo a highly choreographed cascade of events that has both exogenous (e. Read More

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Histone H3K27 demethylase KDM6A is an epigenetic gatekeeper of mTORC1 signalling in cancer.

Gut 2021 Sep 11. Epub 2021 Sep 11.

Helmholtz-University Group "Cell Plasticity and Epigenetic Remodeling", German Cancer Research Center (DKFZ) & Institute of Pathology, University Hospital, Heidelberg, Germany

Objective: Large-scale genome sequencing efforts of human tumours identified epigenetic modifiers as one of the most frequently mutated gene class in human cancer. However, how these mutations drive tumour development and tumour progression are largely unknown. Here, we investigated the function of the histone demethylase KDM6A in gastrointestinal cancers, such as liver cancer and pancreatic cancer. Read More

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September 2021

Inhibition of the MAP2K7-JNK pathway with 5Z-7-oxozeaenol induces apoptosis in T-cell acute lymphoblastic leukemia.

Oncotarget 2021 Aug 31;12(18):1787-1801. Epub 2021 Aug 31.

Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric leukemia with a worse prognosis than most frequent B-cell ALL due to a high incidence of treatment failures and relapse. Our previous work showed that loss of the pioneer factor KLF4 in a NOTCH1-induced T-ALL mouse model accelerated the development of leukemia through expansion of leukemia-initiating cells and activation of the MAP2K7 pathway. Similarly, epigenetic silencing of the gene in children with T-ALL was associated with MAP2K7 activation. Read More

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miRNAs as Regulators of the Early Local Response to Burn Injuries.

Int J Mol Sci 2021 Aug 26;22(17). Epub 2021 Aug 26.

Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, 8036 Graz, Austria.

In burn injuries, risk factors and limitations to treatment success are difficult to assess clinically. However, local cellular responses are characterized by specific gene-expression patterns. MicroRNAs (miRNAs) are single-stranded, non-coding RNAs that regulate mRNA expression on a posttranscriptional level. Read More

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Cysteine derivatives as acetyl lysine mimics to inhibit zinc-dependent histone deacetylases for treating cancer.

Eur J Med Chem 2021 Aug 27;225:113799. Epub 2021 Aug 27.

State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, School of Basic Medicine, Guizhou Medical University, Guiyang, 550004, China. Electronic address:

Zinc-dependent histone deacetylases (HDACs) are important epigenetic regulators that have become important drug targets for treating cancer. Although five HDAC inhibitors have been approved for treating several cancers, there is still a huge demand on discovering new HDAC inhibitors to explore the therapeutic potentials for treating solid tumor cancers. Substrate mimics are a powerful rational design approach for the development of potent inhibitors. Read More

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LncRNA NEAT1 controls the lineage fates of BMSCs during skeletal aging by impairing mitochondrial function and pluripotency maintenance.

Cell Death Differ 2021 Sep 8. Epub 2021 Sep 8.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, Jiangsu Province, China.

Aged bone marrow mesenchymal stem cells (BMSCs) exhibit aberrant self-renewal and lineage specification, which contribute to imbalanced bone-fat and progressive bone loss. In addition to known master regulators of lineage commitment, it is crucial to identify pivotal switches governing the specific differentiation fate of aged BMSCs. Here, we profiled differences in epigenetic regulation between adipogenesis and osteogenesis and identified super-enhancer associated lncRNA nuclear-enriched abundant transcript 1 (NEAT1) as a key bone-fat switch in aged BMSCs. Read More

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September 2021

Clinico-genomic profiling and clonal dynamic modeling of -aberrant myelodysplastic syndrome and acute myeloid leukemia.

Leuk Lymphoma 2021 Sep 9:1-13. Epub 2021 Sep 9.

Department of Medicine-Hematology & Oncology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, MA, USA.

-aberrant myelodysplastic syndrome and acute myeloid leukemia have dismal outcomes. Here, we define the clinico-genomic landscape of disruptions in 40 patients and employ clonal dynamic modeling to map the mutational hierarchy against clinical outcomes. Most mutations (45. Read More

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September 2021

Nonredundant, isoform-specific roles of HDAC1 in glioma stem cells.

JCI Insight 2021 Sep 8;6(17). Epub 2021 Sep 8.

Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, Arizona, USA.

Glioblastoma (GBM) is characterized by an aberrant yet druggable epigenetic landscape. One major family of epigenetic regulators, the histone deacetylases (HDACs), are considered promising therapeutic targets for GBM due to their repressive influences on transcription. Although HDACs share redundant functions and common substrates, the unique isoform-specific roles of different HDACs in GBM remain unclear. Read More

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September 2021

METTL3-mediated RNA m6A hypermethylation promotes tumorigenesis and GH secretion of pituitary somatotroph adenomas.

J Clin Endocrinol Metab 2021 Sep 7. Epub 2021 Sep 7.

Department of Neurosurgery, China Pituitary Disease Registry Center, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.

Introduction: Pituitary growth hormone (GH)-secreting adenomas (GH-PAs) cause mass effects and dysregulated hypersecretion of GH. However, somatic mutation burden is low in PAs. While progress has been made in identifying the epigenetic changes involved in GH-PA initiation, the precise details of its tumorigenesis in GH-PA patients remains to be elucidated. Read More

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September 2021

Oxidative Stress-Induced Ferroptosis in Cardiovascular Diseases and Epigenetic Mechanisms.

Front Cell Dev Biol 2021 19;9:685775. Epub 2021 Aug 19.

Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

The recently discovered ferroptosis is a new kind of iron-regulated cell death that differs from apoptosis and necrosis. Ferroptosis can be induced by an oxidative stress response, a crucial pathological process implicated in cardiovascular diseases (CVDs). Accordingly, mounting evidence shows that oxidative stress-induced ferroptosis plays a pivotal role in angio-cardiopathy. Read More

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CRISPR/SpCas9-mediated double knockout of barley Microrchidia MORC1 and MORC6a reveals their strong involvement in plant immunity, transcriptional gene silencing and plant growth.

Plant Biotechnol J 2021 Sep 6. Epub 2021 Sep 6.

Institute of Phytopathology, Research Centre for BioSystems, Land Use and Nutrition, Justus Liebig University Giessen, Giessen, Germany.

The Microrchidia (MORC) family proteins are important nuclear regulators in both animals and plants with critical roles in epigenetic gene silencing and genome stabilization. In the crop plant barley (Hordeum vulgare), seven MORC gene family members have been described. While barley HvMORC1 has been functionally characterized, very little information is available about other HvMORC paralogs. Read More

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September 2021

Coordination of EZH2 and SOX2 specifies human neural fate decision.

Cell Regen 2021 Sep 6;10(1):30. Epub 2021 Sep 6.

CAS Key Laboratory of Regenerative Biology, Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Hong Kong, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.

Polycomb repressive complexes (PRCs) are essential in mouse gastrulation and specify neural ectoderm in human embryonic stem cells (hESCs), but the underlying molecular basis remains unclear. Here in this study, by employing an array of different approaches, such as gene knock-out, RNA-seq, ChIP-seq, et al., we uncover that EZH2, an important PRC factor, specifies the normal neural fate decision through repressing the competing meso/endoderm program. Read More

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September 2021

Time-course miRNA alterations and SIRT1 inhibition triggered by adolescent lead exposure in mice.

Toxicol Res (Camb) 2021 Aug 7;10(4):667-676. Epub 2021 Jun 7.

Department of Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.

Sirtuin 1 (SIRT1), the NAD-dependent histone deacetylase, has been extensively investigated due to its cognitive protective effect. Studies suggest microRNAs (miRNAs) and histone modifications are key epigenetic regulators of gene expression and play important role in brain development. We previously showed that cognitive impairment by lead (Pb) was associated with downregulation of SIRT1, but the epigenetic role of this is unclear. Read More

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Role of the MOZ/MLL-mediated transcriptional activation system for self-renewal in normal hematopoiesis and leukemogenesis.

Akihiko Yokoyama

FEBS J 2021 Sep 5. Epub 2021 Sep 5.

Tsuruoka Metabolomics Laboratory, National Cancer Center, Tsuruoka, Japan.

Homeostasis in the blood system is maintained by the balance between self-renewing stem cells and nonstem cells. To promote self-renewal, transcriptional regulators maintain epigenetic information during multiple rounds of cell division. Mutations in such transcriptional regulators cause aberrant self-renewal, leading to leukemia. Read More

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September 2021

DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation.

Cell Mol Life Sci 2021 Sep 5. Epub 2021 Sep 5.

Department of Neuroscience, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.

The differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes is the prerequisite for remyelination in demyelinated disorders such as multiple sclerosis (MS). Epigenetic mechanisms, such as DNA methylation, have been suggested to control the intricate network of transcription factors involved in OPC differentiation. Yet, the exact mechanism remains undisclosed. Read More

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September 2021

Factors regulating dynamics of angiotensin-converting enzyme-2 (ACE2), the gateway of SARS-CoV-2: Epigenetic modifications and therapeutic interventions by epidrugs.

Biomed Pharmacother 2021 Aug 30;143:112095. Epub 2021 Aug 30.

Centre of Excellence in Integrated Omics and Computational Biology, Utkal University, Bhubaneswar 751004, Odisha, India; Post-Graduate Department of Biotechnology, Utkal University, Bhubaneswar 751004, Odisha, India. Electronic address:

Angiotensin-converting enzyme-2 (ACE2) is one of the major components of the renin-angiotensin system (RAS) and participates in the physiological functions of the cardiovascular system and lungs. Recent studies identified ACE2 as the receptor for the S-protein of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and thus acts as the gateway for viral entry into the human body. Virus infection causes an imbalance in the RAS axis and induces acute lungs injury and fibrosis. Read More

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The ATPase SRCAP is associated with the mitotic apparatus, uncovering novel molecular aspects of Floating-Harbor syndrome.

BMC Biol 2021 Sep 2;19(1):184. Epub 2021 Sep 2.

Dipartimento di Biologia e Biotecnologie "Charles Darwin" Sapienza Università di Roma, Via dei Sardi, 70, Roma, Italy.

Background: A variety of human genetic diseases is known to be caused by mutations in genes encoding chromatin factors and epigenetic regulators, such as DNA or histone modifying enzymes and members of ATP-dependent chromatin remodeling complexes. Floating-Harbor syndrome is a rare genetic disease affecting human development caused by dominant truncating mutations in the SRCAP gene, which encodes the ATPase SRCAP, the core catalytic subunit of the homonymous chromatin-remodeling complex. The main function of the SRCAP complex is to promote the exchange of histone H2A with the H2A. Read More

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September 2021

Predictive value of m5C regulatory gene expression in pancreatic adenocarcinoma.

Sci Rep 2021 Sep 1;11(1):17529. Epub 2021 Sep 1.

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People's Republic of China.

Pancreatic adenocarcinoma (PAAD) is the most malignant digestive tumor. The global incidence of pancreatic cancer has been rapidly trending upwards, necessitating an exploration of potential prognostic biomarkers and mechanisms of disease development. One of the most prevalent RNA modifications is 5-methylcytosine (m5C); however, its contribution to PAAD remains unclear. Read More

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September 2021

Histone deacetylase HDA-4-mediated epigenetic regulation in space-flown C. elegans.

NPJ Microgravity 2021 Sep 1;7(1):33. Epub 2021 Sep 1.

Human Spaceflight Technology Directorate, Japan Aerospace Exploration Agency, Tsukuba, Ibaraki, Japan.

Epigenetic changes during long-term spaceflight are beginning to be studied by NASA's twin astronauts and other model organisms. Here, we evaluate the epigenetic regulation of gene expression in space-flown C. elegans by comparing wild type and histone deacetylase (hda)-4 mutants. Read More

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September 2021

Transcriptome-wide mA methylome during osteogenic differentiation of human adipose-derived stem cells.

Stem Cell Res Ther 2021 Sep 1;12(1):489. Epub 2021 Sep 1.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, China.

Objectives: Adipose-derived stem cells are frequently used for bone regeneration both in vitro and in vivo. N-methyladenosine (mA) is the most abundant post-transcriptional modification on eukaryotic RNAs and plays multifaceted roles in development and diseases. However, the regulatory mechanisms of mA in osteogenic differentiation of human adipose-derived stem cells (hASCs) remain elusive. Read More

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September 2021

High-quality genome assembly of 'Cuiguan' pear (Pyrus pyrifolia) as a reference genome for identifying regulatory genes and epigenetic modifications responsible for bud dormancy.

Hortic Res 2021 Sep 1;8(1):197. Epub 2021 Sep 1.

College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, Zhejiang, 310058, China.

Dormancy-associated MADS-box (DAM) genes serve as crucial regulators of the endodormancy cycle in rosaceous plants. Although pear DAM genes have been identified previously, the lack of a high-quality reference genome and techniques to study gene function have prevented accurate genome-wide analysis and functional verification of such genes. Additionally, the contribution of other genes to the regulation of endodormancy release remains poorly understood. Read More

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September 2021

Targeting enhancer reprogramming to mitigate MEK inhibitor resistance in preclinical models of advanced ovarian cancer.

J Clin Invest 2021 Aug 31. Epub 2021 Aug 31.

State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.

Ovarian cancer is characterized by aberrant activation of the mitogen-activated protein kinase (MAPK), highlighting the importance of targeting the MAPK pathway as an attractive therapeutic strategy. However, the clinical efficacy of MEK inhibitors is limited due to intrinsic or acquired drug resistance. Here, we established patient-derived ovarian cancer models resistant to MEK inhibitors and demonstrated that resistance to the clinically-approved MEK inhibitor trametinib was associated with enhancer reprogramming. Read More

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Targeting the Atf7ip-Setdb1 complex augments antitumor immunity by boosting tumor immunogenicity.

Cancer Immunol Res 2021 Aug 30. Epub 2021 Aug 30.

State Key Laboratory of Cell Biology, CAS center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences.

Substantial progress has been made in understanding how tumors escape immune surveillance. However, few measures to counteract tumor immune evasion have been developed. Suppression of tumor antigen expression is a common adaptive mechanism that cancers use to evade detection and destruction by the immune system. Read More

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Epigenetics in kidney diseases.

Adv Clin Chem 2021 21;104:233-297. Epub 2020 Oct 21.

Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, United States. Electronic address:

Epigenetics examines heritable changes in DNA and its associated proteins except mutations in gene sequence. Epigenetic regulation plays fundamental roles in kidney cell biology through the action of DNA methylation, chromatin modification via epigenetic regulators and non-coding RNA species. Kidney diseases, including acute kidney injury, chronic kidney disease, diabetic kidney disease and renal fibrosis are multistep processes associated with numerous molecular alterations even in individual kidney cells. Read More

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October 2020

m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma.

Aging (Albany NY) 2021 Aug 30;13(16):20698-20715. Epub 2021 Aug 30.

Department of Pharmacy, Gaozhou People's Hospital, Gaozhou 525200, China.

Background: There is increasing evidence of the epigenetic regulation of the immune response in cancer. However, the specific functions and mechanisms of RNA N6-methyladenosine (m6A) modification in the cell infiltration in the hepatocellular carcinoma (HCC) tumor microenvironment (TME) is unknown.

Methods: We systematically analyzed the m6A-modification patterns of 371 HCC samples based on 23 m6A regulators, and determined their correlation with TME cell-infiltrating characteristics. Read More

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