92,754 results match your criteria transcriptional activation

Inhibition of mTOR by rapamycin does not improve hypoxic pulmonary hypertension-induced right heart failure in old mice.

Exp Gerontol 2021 May 7:111395. Epub 2021 May 7.

Division of Kinesiology & Health, University of Wyoming, Laramie, WY, United States of America. Electronic address:

Inhibition of the mammalian target of rapamycin (mTOR) by rapamycin attenuates heart failure (HF) and age-associated changes in left ventricular (LV) function. Rapamycin has also been suggested as a therapy for pulmonary hypertension (PH) and concomitant right heart failure (PH-RHF) based on reports of elevated mTOR signaling in young models with PH. However, rapamycin has yet to be tested in the setting of aging, PH, and right heart disease despite the fact that RV function predicts survival in both age-related HF as well as several pulmonary disease states including PH. Read More

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Macrophage activation in the lung during the progression of nitrogen mustard induced injury is associated with histone modifications and altered miRNA expression.

Toxicol Appl Pharmacol 2021 May 7:115569. Epub 2021 May 7.

Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, 08854, USA; Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ 08854, USA. Electronic address:

Activated macrophages have been implicated in lung injury and fibrosis induced by the cytotoxic alkylating agent, nitrogen mustard (NM). Herein, we determined if macrophage activation is associated with histone modifications and altered miRNA expression. Treatment of rats with NM (0. Read More

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Myeloid lncRNA LOUP Mediates Opposing Regulatory Effects of RUNX1 and RUNX1-ETO in t(8;21) AML.

Blood 2021 May 10. Epub 2021 May 10.

Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, MA, 02115, USA, United States.

The mechanism underlying cell type-specific gene induction conferred by ubiquitous transcription factors as well as disruptions caused by their chimeric derivatives in leukemia is not well understood. Here we investigate whether RNAs coordinate with transcription factors to drive myeloid gene transcription. In an integrated genome-wide approach surveying for gene loci exhibiting concurrent RNA- and DNA-interactions with the broadly expressed transcription factor RUNX1, we identified the long noncoding RNA LOUP. Read More

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Overexpression of wild type IL-7Rα promotes T-cell acute lymphoblastic leukemia/lymphoma.

Blood 2021 May 10. Epub 2021 May 10.

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.

Tight regulation of IL-7Rα expression is essential for normal T-cell development. IL-7Rα gain-of-function mutations are known drivers of T-cell acute lymphoblastic leukemia (T-ALL). Although a subset of T-ALL patients display very high IL7R mRNA levels and cases with IL7R gains have been reported, the impact of IL-7Rα overexpression, rather than mutational activation, on leukemogenesis remains unclear. Read More

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Role of CCR2 Myeloid Cells in Inflammation Responses Driven by Expression of a Surfactant Protein-C Mutant in the Alveolar Epithelium.

Front Immunol 2021 22;12:665818. Epub 2021 Apr 22.

Pulmonary, Allergy, and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

Acute inflammatory exacerbations (AIE) represent precipitous deteriorations of a number of chronic lung conditions, including pulmonary fibrosis (PF), chronic obstructive pulmonary disease and asthma. AIEs are marked by diffuse and persistent polycellular alveolitis that profoundly accelerate lung function decline and mortality. In particular, excess monocyte mobilization during AIE and their persistence in the lung have been linked to poor disease outcome. Read More

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Transcriptional Profiles of Genes Related to Stress and Immune Response in Rainbow Trout () Symptomatically or Asymptomatically Infected With .

Front Immunol 2021 21;12:639489. Epub 2021 Apr 21.

Key Laboratory of Mariculture (Ocean University of China), Ministry of Education (KLMME), Ocean University of China, Qingdao, China.

Rainbow trout () is one of the most common aquaculture fish species worldwide. Vibriosis disease outbreaks cause significant setbacks to aquaculture. The stress and immune responses are bidirectionally modulated in response to the health challenges. Read More

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Endocrine disrupting potential of veterinary drugs by in vitro stably transfected human androgen receptor transcriptional activation assays.

Environ Pollut 2021 Apr 30;286:117201. Epub 2021 Apr 30.

Department of Food Science and Biotechnology, Chung-Ang University, Anseong, 17546, Republic of Korea. Electronic address:

We describe the androgen receptor (AR) agonistic/antagonistic effects of 140 veterinary drugs regulated in Republic of Korea, by setting maximum residue limits. It was conducted using two in vitro test guidelines of the Organization for Economic Cooperation and Development (OECD)-the AR-EcoScreen AR transactivation (TA) assay and the 22Rv1/MMTV_GR-KO AR TA assay. These were performed alongside the AR binding affinity assay to confirm whether their AR agonistic/antagonistic effects are based on the binding affinity to AR. Read More

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Regulation of GC box activity by 8-oxoguanine.

Redox Biol 2021 Apr 30;43:101997. Epub 2021 Apr 30.

Unit "Responses to DNA Lesions", Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, 55131, Germany; Institute of Nutritional Science, University of Jena, Jena, 07743, Germany. Electronic address:

The oxidation-induced DNA modification 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) was recently implicated in the activation and repression of gene transcription. We aimed at a systematic characterisation of the impacts of 8-oxodG on the activity of a GC box placed upstream from the RNA polymerase II core promoter. With the help of reporters carrying single synthetic 8-oxodG residues at four conserved G:C base pairs (underlined) within the 5'-TGGGCGGAGC-3' GC box sequence, we identified two modes of interference of 8-oxodG with the promoter activity. Read More

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Phthalates promote the invasion of hepatocellular carcinoma cells by enhancing the interaction between Pregnane X receptor and E26 transformation specific sequence 1.

Pharmacol Res 2021 May 6:105648. Epub 2021 May 6.

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, P.R. China. Electronic address:

Phthalates (PAEs) are considered endocrine-disrupting chemicals (EDCs), a series of compounds able to disrupt the normal regulation of the human endocrine-system. In the present study, we investigated the roles of four PAEs, butyl benzyl phthalate (BBP), dibutyl phthalate (DBP), dimethyl phthalate (DMP), and diethyl phthalate (DEP), in hepatocellular carcinoma (HCC) cells. We define novel roles for the PAEs on the migration of HCC cells via their enhancing of the interaction between the pregnane X receptor (PXR) and E26 transformation specific sequence 1 (ETS-1). Read More

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Pharmacological Inhibition of GLUT1 As a New Immunotherapeutic Approach After Myocardial Infarction.

Biochem Pharmacol 2021 May 6:114597. Epub 2021 May 6.

Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany. Electronic address:

Myocardial infarction (MI) is one of the major contributors to cardiovascular morbidity and mortality. Excess inflammation significantly contributes to cardiac remodeling and heart failure after MI. Accumulating evidence has shown the central role of cellular metabolism in regulating the differentiation and function of cells. Read More

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Identification of pseudolaric acid B as a novel Hedgehog pathway inhibitor in medulloblastoma.

Biochem Pharmacol 2021 May 5:114593. Epub 2021 May 5.

Institute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Research Center of Chinese Herbal Resources Science and Engineering, School of Pharmaceutical Sciences, Key Laboratory of Chinese Medicinal Resource from Lingnan, Ministry of Education, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address:

Aberrant activation of the Hedgehog (Hh) pathway is implicated in the pathogenesis and development of multiple cancers, especially Hh-driven medulloblastoma (MB). Smoothened (SMO) is a promising therapeutic target of the Hh pathway in clinical cancer treatment. However, SMO mutations frequently occur, which leads to drug resistance and tumor relapse. Read More

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Characterization of a transcription factor SlNAC7 gene from Suaeda liaotungensis and its role in stress tolerance.

J Plant Res 2021 May 8. Epub 2021 May 8.

School of Life Sciences, Liaoning Normal University, Dalian, 116081, China.

NAC (NAM, ATAF1/2, CUC2) transcription factors play important roles in plant growth, development, and responses to abiotic stress. In this study, we cloned an NAC2 subfamily transcription factor gene (SlNAC7) from the halophyte Suaeda liaotungensis K., and conducted a series of studies to determine the characteristics and functions of this gene. Read More

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Upregulation of Nogo-B by HIF-1 and AP-1 in hepatocellular carcinoma.

Cancer Sci 2021 May 8. Epub 2021 May 8.

Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, 200062, China.

Nogo-B is an important regulator of tumor angiogenesis. Expression of Nogo-B is remarkably upregulated in multiple tumor types, especially hepatocellular carcinoma (HCC). Here, we show the transcriptional regulation mechanisms of Nogo-B in liver cancer. Read More

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Low nitrogen conditions accelerate flowering by modulating the phosphorylation state of FLOWERING BHLH 4 in .

Proc Natl Acad Sci U S A 2021 May;118(19)

Faculty of Science, Graduate School of Life Science, Hokkaido University, Sapporo 060-0810, Japan;

Nitrogen (N) is an essential nutrient that affects multiple plant developmental processes, including flowering. As flowering requires resources to develop sink tissues for reproduction, nutrient availability is tightly linked to this process. Low N levels accelerate floral transition; however, the molecular mechanisms underlying this response are not well understood. Read More

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Actions and interactions of IGF-I and MMPs during muscle regeneration.

Semin Cell Dev Biol 2021 May 4. Epub 2021 May 4.

Applied Physiology & Kinesiology, College of Health and Human Performance, University of Florida, 1864 Stadium Road, Gainesville, FL 32611, USA. Electronic address:

Muscle regeneration requires the coordination of several factors to mobilize satellite cells and macrophages, remodel the extracellular matrix surrounding muscle fibers, and repair existing and/or form new muscle fibers. In this review, we focus on insulin-like growth factor I and the matrix metalloproteinases, which are secreted proteins that act on cells and the matrix to resolve damage. While their actions appear independent, their interactions occur at the transcriptional and post-translational levels to promote feed-forward activation of each other. Read More

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TIRR inhibits the 53BP1-p53 complex to alter cell-fate programs.

Mol Cell 2021 Apr 29. Epub 2021 Apr 29.

Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address:

53BP1 influences genome stability via two independent mechanisms: (1) regulating DNA double-strand break (DSB) repair and (2) enhancing p53 activity. We discovered a protein, Tudor-interacting repair regulator (TIRR), that associates with the 53BP1 Tudor domain and prevents its recruitment to DSBs. Here, we elucidate how TIRR affects 53BP1 function beyond its recruitment to DSBs and biochemically links the two distinct roles of 53BP1. Read More

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Overexpression of oncogenic H-Ras in hTERT-immortalized and SV40-transformed human cells targets replicative and specialized DNA polymerases for depletion.

PLoS One 2021 7;16(5):e0251188. Epub 2021 May 7.

Department of Pathology, The Jake Gittlen Laboratories for Cancer Research, Penn State University College of Medicine, Hershey, Pennsylvania, United States of America.

DNA polymerases play essential functions in replication fork progression and genome maintenance. DNA lesions and drug-induced replication stress result in up-regulation and re-localization of specialized DNA polymerases η and κ. Although oncogene activation significantly alters DNA replication dynamics, causing replication stress and genome instability, little is known about DNA polymerase expression and regulation in response to oncogene activation. Read More

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Computational modeling of gene-specific transcriptional repression, activation and chromatin interactions in leukemogenesis by LASSO-regularized logistic regression.

IEEE/ACM Trans Comput Biol Bioinform 2021 May 7;PP. Epub 2021 May 7.

Many physiological and pathological pathways are dependent on gene-specific on/off regulation of transcription. Some genes are repressed, while others are activated. Although many previous studies have analyzed the mechanisms of gene-specific repression and activation, these studies are mainly based on the use of candidate genes, which are either repressed or activated, without simultaneously comparing and contrasting both groups of genes. Read More

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The Ca -binding protein sorcin stimulates transcriptional activity of the unfolded protein response mediator ATF6.

FEBS Lett 2021 May 7. Epub 2021 May 7.

Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion & Reproduction, Imperial College London, UK.

Sorcin is a calcium-binding protein involved in maintaining endoplasmic reticulum (ER) Ca stores. We have previously shown that overexpressing sorcin under the rat insulin promoter was protective against high fat diet-induced pancreatic beta cell dysfunction in vivo. Activating Transcription Factor 6 (ATF6) is a key mediator of the unfolded protein response (UPR) that provides cellular protection during the progression of ER stress. Read More

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The chromatin remodelling protein LSH/HELLS regulates the amount and distribution of DNA hydroxymethylation in the genome.

Epigenetics 2021 May 7:1-22. Epub 2021 May 7.

Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB-Cancer Research Centre (U-CRC), Université Libre De Bruxelles, Brussels, Belgium.

Ten-Eleven Translocation (TET) proteins convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) leading to a dynamic epigenetic state of DNA that can influence transcription and chromatin organization. While TET proteins interact with complexes involved in transcriptional repression and activation, the overall understanding of the molecular mechanisms involved in TET-mediated regulation of gene expression still remains limited. Here, we show that TET proteins interact with the chromatin remodelling protein lymphoid-specific helicase (LSH/HELLS) and . Read More

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A domesticated Harbinger transposase forms a complex with HDA6 and promotes histone H3 deacetylation at genes but not TEs in Arabidopsis.

J Integr Plant Biol 2021 May 6. Epub 2021 May 6.

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.

In eukaryotes, histone acetylation is a major modification on histone N-terminal tails that is tightly connected to transcriptional activation. HDA6 is a histone deacetylase involved in the transcriptional regulation of genes and transposable elements (TEs) in Arabidopsis thaliana. HDA6 has been shown to participate in several complexes in plants, including a conserved SIN3 complex. Read More

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Cyclic AMP-dependent activation of ERK via GLP-1 receptor signalling requires the neuroendocrine cell-specific guanine nucleotide exchanger NCS-RapGEF2.

J Neuroendocrinol 2021 May 6:e12974. Epub 2021 May 6.

Section on Molecular Neuroscience, National Institute of Mental Health - Intramural Research Program, Bethesda, MD, USA.

Cyclic AMP activation of the Rap-Braf-MEK-ERK pathway after signalling initiated by the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP), via the G -protein coupled receptor (G PCR) PAC1, occurs uniquely through the neuritogenic cAMP sensor Rap guanine nucleotide exchange factor 2 (NCS-RapGEF2) in Neuroscreen-1 (NS-1) neuroendocrine cells. We examined the expression of other Family B G PCRs in this cell line and assessed cAMP elevation and neuritogenesis after treatment with their cognate peptide ligands. Exposure of NS-1 cells to the VIPR1/2 agonist vasoactive intestinal polypeptide, or the GLP1R agonist exendin-4, did not induce neuritogenesis, or elevation of cAMP, presumably as a result of insufficient receptor protein expression. Read More

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Bone marrow mesenchymal stromal cells in chronic myelomonocytic leukaemia: overactivated WNT/β-catenin signalling by parallel RNA sequencing and dysfunctional phenotypes.

Br J Haematol 2021 May 6. Epub 2021 May 6.

Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080, P.R. China.

Sophisticated cross-talk between bone marrow mesenchymal stromal cells (BM MSCs) and haematopoietic/leukaemic stem cells in patients with myelodysplastic syndromes (MDS) and myeloid leukaemia have been emphasized in previous reports. However, mesenchymal elements in patients with chronic myelomonocytic leukaemia (CMML) were poorly investigated. By utilizing a parallel RNA-sequencing method, we investigated the transcriptional profile and functional defects of primary BM MSCs from patients with CMML for the first time. Read More

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MicroRNA-26 regulates the expression of CTGF after exposure to ionizing radiation.

Radiat Environ Biophys 2021 May 6. Epub 2021 May 6.

Department of Matrix Biology and Medicine, Faculty of Medicine, Oita University, Oita, Japan.

Radiation-induced fibrosis (RIF) is a serious complication that occurs after irradiation and which is caused by the deposition of extracellular matrix (ECM) proteins such as collagen. However, the underlying mechanisms, including the expression of the cytokines, that promote the RIF process, are not yet fully understood. MicroRNAs (miRNAs) have recently been suggested to act as post-transcriptional repressors for many genes; however, their role in the process of RIF remains to be elucidated. Read More

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Sweet Melody or Jazz? Transcription Around DNA Double-Strand Breaks.

Front Mol Biosci 2021 20;8:655786. Epub 2021 Apr 20.

Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.

Genomic integrity is continuously threatened by thousands of endogenous and exogenous damaging factors. To preserve genome stability, cells developed comprehensive DNA damage response (DDR) pathways that mediate the recognition of damaged DNA lesions, the activation of signaling cascades, and the execution of DNA repair. Transcription has been understood to pose a threat to genome stability in the presence of DNA breaks. Read More

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Chromatin Modifiers in Transcriptional Regulation: New Findings and Prospects.

Acta Naturae 2021 Jan-Mar;13(1):16-30

Institute of Gene Biology RAS, Group of transcriptional complexes dynamics, Moscow, 119334 Russia.

Histone-modifying and remodeling complexes are considered the main coregulators that affect transcription by changing the chromatin structure. Coordinated action by these complexes is essential for the transcriptional activation of any eukaryotic gene. In this review, we discuss current trends in the study of histone modifiers and chromatin remodelers, including the functional impact of transcriptional proteins/ complexes i. Read More

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Targeting non-canonical activation of GLI1 by the SOX2-BRD4 transcriptional complex improves the efficacy of HEDGEHOG pathway inhibition in melanoma.

Oncogene 2021 May 6. Epub 2021 May 6.

Core Research Laboratory - Institute for Cancer Research and Prevention (ISPRO), Florence, Italy.

Despite the development of new targeted and immune therapies, the prognosis of metastatic melanoma remains bleak. Therefore, it is critical to better understand the mechanisms controlling advanced melanoma to develop more effective treatment regimens. Hedgehog/GLI (HH/GLI) signaling inhibitors targeting the central pathway transducer Smoothened (SMO) have shown to be clinical efficacious in skin cancer; however, several mechanisms of non-canonical HH/GLI pathway activation limit their efficacy. Read More

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TORC1 regulates the transcriptional response to glucose and developmental cycle via the Tap42-Sit4-Rrd1/2 pathway in Saccharomyces cerevisiae.

BMC Biol 2021 May 6;19(1):95. Epub 2021 May 6.

Bioinformatics Institute, 30 Biopolis Street, Singapore, 138671, Singapore.

Background: Target of Rapamycin Complex 1 (TORC1) is a highly conserved eukaryotic protein complex that couples the presence of growth factors and nutrients in the environment with cellular proliferation. TORC1 is primarily implicated in linking amino acid levels with cellular growth in yeast and mammals. Although glucose deprivation has been shown to cause TORC1 inactivation in yeast, the precise role of TORC1 in glucose signaling and the underlying mechanisms remain unclear. Read More

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Identification of juvenile hormone-induced posttranslational modifications of methoprene tolerant and Krüppel homolog 1 in the yellow fever mosquito, Aedes aegypti.

J Proteomics 2021 May 3:104257. Epub 2021 May 3.

Department of Entomology, College of Agriculture, Food and Environment, University of Kentucky, S-225 Agricultural Science Center North Lexington, KY 40546-0091, United States. Electronic address:

Recent studies reported that JH regulated phosphorylation status of the JH-receptor complex contributes to its transcription activity in Aedes aegypti. However, phosphorylation sites of these proteins have not yet been identified. In this study, we found that the fusion of an EGFP tag to Ae. Read More

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Decoding dynamic epigenetic landscapes in human oocytes using single-cell multi-omics sequencing.

Cell Stem Cell 2021 Apr 27. Epub 2021 Apr 27.

Center for Translational Medicine, Ministry of Education Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China. Electronic address:

Developing female human germ cells undergo genome-wide epigenetic reprogramming, but de novo DNA methylation dynamics and their interplay with chromatin states and transcriptional activation in developing oocytes is poorly understood. Here, we developed a single-cell multi-omics sequencing method, scChaRM-seq, that enables simultaneous profiling of the DNA methylome, transcriptome, and chromatin accessibility in single human oocytes and ovarian somatic cells. We observed a global increase in DNA methylation during human oocyte growth that correlates with chromatin accessibility, whereas increases of DNA methylation at specific features were associated with active transcription. Read More

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