8,709 results match your criteria lysine methylation

A Non-Dicer RNase III and Four Other Novel Factors Required for RNAi-Mediated Transposon Suppression in the Human Pathogenic Yeast Cryptococcus neoformans.

G3 (Bethesda) 2019 Jul;9(7):2235-2244

Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, Chan-Zuckerberg Biohub, San Francisco, CA 94158.

The human pathogenic yeast Cryptococcus neoformans silences transposable elements using endo-siRNAs and an Argonaute, Ago1. Endo-siRNAs production requires the RNA-dependent RNA polymerase, Rdp1, and two partially redundant Dicer enzymes, Dcr1 and Dcr2, but is independent of histone H3 lysine 9 methylation. We describe here an insertional mutagenesis screen for factors required to suppress the mobilization of the C. Read More

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Genome-wide analysis of SET-domain group histone methyltransferases in apple reveals their role in development and stress responses.

BMC Genomics 2021 Apr 19;22(1):283. Epub 2021 Apr 19.

State Key Laboratory of Crop Stress Biology for Arid Areas/Shaanxi Key Laboratory of Apple, College of Horticulture, Northwest A&F University, Yangling, 712100, Shaanxi, China.

Background: Histone lysine methylation plays an important role in plant development and stress responses by activating or repressing gene expression. Histone lysine methylation is catalyzed by a class of SET-domain group proteins (SDGs). Although an increasing number of studies have shown that SDGs play important regulatory roles in development and stress responses, the functions of SDGs in apple remain unclear. Read More

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Dynamic Histone H3 Modifications Regulate Meiosis Initiation via Respiration.

Front Cell Dev Biol 2021 1;9:646214. Epub 2021 Apr 1.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, College of Life Sciences, University of Chinese Academy of Sciences, Stem Cell and Regenerative Medicine Innovation Institute, Chinese Academy of Sciences, Beijing, China.

Meiosis is essential for genetic stability and diversity during sexual reproduction in most eukaryotes. Chromatin structure and gene expression are drastically changed during meiosis, and various histone modifications have been reported to participate in this unique process. However, the dynamic of histone modifications during meiosis is still not well investigated. Read More

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Drosophila NSD deletion induces developmental anomalies similar to those seen in Sotos syndrome 1 patients.

Genes Genomics 2021 Apr 17. Epub 2021 Apr 17.

Department of Biological Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea.

Background: Haploinsufficiency of the human nuclear receptor binding suppressor of variegation 3-9, enhancer of zeste, and trithorax (SET) domain 1 (NSD1) gene causes a developmental disorder called Sotos syndrome 1 (SOTOS1), which is associated with overgrowth and macrocephaly. NSD family proteins encoding histone H3 lysine 36 (H3K36) methyltransferases are conserved in many species, and Drosophila has a single NSD homolog gene, NSD.

Objective: To gain insight into the biological functions of NSD1 deficiency in the developmental anomalies seen in SOTOS1 patients using an NSD-deleted Drosophila mutant. Read More

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Aberrant Epigenetic Reprogramming in the First Cell Cycle of Bovine Somatic Cell Nuclear Transfer Embryos.

Cell Reprogram 2021 Apr;23(2):99-107

Affiliated Hospital of Shaanxi University of Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China.

Zygotic epigenetic reprogramming is the major initial event in embryo development to acquire a totipotent potential. However, the patterns of epigenetic modifications in bovine zygote were not well clarified, especially in the first cell cycle of bovine somatic cell nuclear transfer (SCNT) embryos. This study was conducted to examine the patterns of DNA methylation (5-methylcytosine [5mc] and 5-hydroxymethylcytosine [5hmc]) and histone H3 lysine 9 methylation (H3K9m2 and H3K9m3) in the first cell cycle of bovine fertilization (IVF) and SCNT embryos. Read More

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The Role of Histone Lysine Methylation in the Response of Mammalian Cells to Ionizing Radiation.

Front Genet 2021 30;12:639602. Epub 2021 Mar 30.

Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy.

Eukaryotic genomes are wrapped around nucleosomes and organized into different levels of chromatin structure. Chromatin organization has a crucial role in regulating all cellular processes involving DNA-protein interactions, such as DNA transcription, replication, recombination and repair. Histone post-translational modifications (HPTMs) have a prominent role in chromatin regulation, acting as a sophisticated molecular code, which is interpreted by HPTM-specific effectors. Read More

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Recruitment of KMT2C/MLL3 to DNA damage sites mediates DNA damage responses and regulates PARP inhibitor sensitivity in cancer.

Cancer Res 2021 Apr 14. Epub 2021 Apr 14.

Department of Cancer Biology, Wake Forest University School of Medicine

When recruited to promoters, histone 3 lysine 4 (H3K4) methyltransferases KMT2 (KMT2A-D) activate transcription by opening chromatin through H3K4 methylation. Here we report that KMT2 mutations occur frequently in non-small cell lung cancer (NSCLC) and are associated with high mutation loads and poor survival. KMT2C regulated DNA damage responses (DDR) through direct recruitment to DNA damage sites by Ago2 and small noncoding DNA damage response RNA, where it mediates H3K4 methylation, chromatin relaxation, secondary recruitment of DDR factors, and amplification of DDR signals along chromatin. Read More

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Establishing RNA-RNA interactions remodels lncRNA structure and promotes PRC2 activity.

Sci Adv 2021 Apr 14;7(16). Epub 2021 Apr 14.

Molecular Biology Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Human Polycomb Repressive Complex 2 (PRC2) catalysis of histone H3 lysine 27 methylation at certain loci depends on long noncoding RNAs (lncRNAs). Yet, in apparent contradiction, RNA is a potent catalytic inhibitor of PRC2. Here, we show that intermolecular RNA-RNA interactions between the lncRNA HOTAIR and its targets can relieve RNA inhibition of PRC2. Read More

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Hypoxic preconditioning induces epigenetic changes and modifies swine mesenchymal stem cell angiogenesis and senescence in experimental atherosclerotic renal artery stenosis.

Stem Cell Res Ther 2021 Apr 14;12(1):240. Epub 2021 Apr 14.

Division of Nephrology and Hypertension, Mayo Clinic, 200, First Street SW, Rochester, MN, 55902, USA.

Background: Atherosclerotic renal artery stenosis (ARAS) is a risk factor for ischemic and hypertensive kidney disease (HKD) for which autologous mesenchymal stem cell (MSC) appears to be a promising therapy. However, MSCs from ARAS patients exhibit impaired function, senescence, and DNA damage, possibly due to epigenetic mechanisms. Hypoxia preconditioning (HPC) exerts beneficial effects on cellular proliferation, differentiation, and gene and protein expression. Read More

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LC-MALDI-TOF ISD MS analysis is an effective, simple and rapid method of investigation for histones characterization: Application to EBV lymphoblastoid cell lines.

J Mass Spectrom 2021 Feb 20;56(5):e4712. Epub 2021 Feb 20.

National Research Council, Institute for Biomedical Research and Innovation (IRIB), Cosenza, Italy.

This contribution is the result of our progressive engagement to develop and to apply a top-down liquid chromatography (LC) matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) (LC-MALDI-TOF) analysis for the histone post-translational modifications (PTMs) and variants characterization, mainly in order to provide comprehensive and fast results. The histone post-translational modifications and the differential expression of the histone variants play an essential role both in the DNA packaging mechanism in chromosomes and in the regulation of gene expression in different cellular processes, also in response to molecular agents of environmental origin. This epigenetic mechanism is widely studied in different field such as cellular differentiation, development and in the understanding of mechanisms underlying diseases. Read More

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February 2021

Systematic analysis of JmjC gene family and stress--response expression of KDM5 subfamily genes in .

PeerJ 2021 31;9:e11137. Epub 2021 Mar 31.

Key Laboratory of Crop Epigenetic Regulation and Development, Hunan Province, Changsha, China.

Background: Jumonji C (JmjC) proteins exert critical roles in plant development and stress response through the removal of lysine methylation from histones. which originated from spontaneous hybridization by and , is the most important oilseed crop after soybean. In JmjC proteins of species, the structure and function and its relationship with the parents and model plant remain uncharacterized. Read More

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An insight into the promoter methylation of PHF20L1 and the gene association with metastasis in breast cancer.

Adv Clin Exp Med 2021 Apr 13. Epub 2021 Apr 13.

Department of Biomedicine, Faculty of Medicine, Meritorious Autonomous University of Puebla (BUAP), Puebla, Mexico.

Background: Plant homeodomain finger protein 20-like 1 (PHF20L1) is a protein reader involved in epigenetic regulation that binds monomethyl-lysine. An oncogenic function has been attributed to PHF20L1 but its role in breast cancer (BC) is not clear.

Objectives: To explore PHF20L1 promoter methylation and comprehensive bioinformatics analysis to improve understanding of the role of PHF20L1 in BC. Read More

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The interplay between DNA and histone methylation: molecular mechanisms and disease implications.

EMBO Rep 2021 Apr 12:e51803. Epub 2021 Apr 12.

Department of Genetics and Development and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.

Methylation of cytosine in CpG dinucleotides and histone lysine and arginine residues is a chromatin modification that critically contributes to the regulation of genome integrity, replication, and accessibility. A strong correlation exists between the genome-wide distribution of DNA and histone methylation, suggesting an intimate relationship between these epigenetic marks. Indeed, accumulating literature reveals complex mechanisms underlying the molecular crosstalk between DNA and histone methylation. Read More

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Past, present, and perspectives of protein N-terminal methylation.

Curr Opin Chem Biol 2021 Apr 8;63:115-122. Epub 2021 Apr 8.

Department of Medicinal Chemistry and Molecular Pharmacology, Purdue Institute for Drug Discovery, Purdue University Center for Cancer Research, Purdue University, 720 Clinic Drive, West Lafayette, IN, 47907, United States. Electronic address:

The posttranslational methylation of the α-N-terminal amino group of proteins was first documented over 40 years ago, but the functional significance of this modification has been underexplored relative to lysine and arginine methylation. Increasing reports implicates α-N-terminal methylation as a widespread and critical regulator of mitosis, chromatin interactions, DNA repair, and translation fidelity. Here, we summarize advances in the current understanding of protein α-N-terminal methylation biological functions and mechanisms across eukaryotic organisms. Read More

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Dynamic association of the H3K64 trimethylation mark with genes encoding exported proteins in Plasmodium falciparum.

J Biol Chem 2021 Apr 8:100614. Epub 2021 Apr 8.

Pathogen Biology group, Rajiv Gandhi Centre for Biotechnology (RGCB), Thycaud PO, Thiruvananthapuram, Kerala, 695014, India. Electronic address:

Epigenetic modifications have emerged as critical regulators of virulence genes and stage-specific gene expression in Plasmodium falciparum. However, the specific roles of histone core epigenetic modifications in regulating the stage-specific gene expression are not well understood. In this study, we report an unconventional trimethylation at lysine 64 on histone 3 (H3K64me3) and characterize its functional relevance in P. Read More

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SNF5 promotes IL-1β Expression via H3K4me1 in Atherosclerosis induced by Homocysteine.

Int J Biochem Cell Biol 2021 Apr 5:105974. Epub 2021 Apr 5.

School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan, 750004, China; Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, 750004, China. Electronic address:

Homocysteine (Hcy) is a strong and independent risk factor of atherosclerosis. It can accelerate atherosclerosis through increased production of inflammatory factors, especially interleukin-1 β (IL-1β), while the precise mechanisms remain to be well elucidated. In this study, we investigated the role of the tumor suppressor gene SNF5 related to Switch/Sucrose Non-Fermentable complex (SWI/SNF) in the occurrence and development of atherosclerosis induced by Hcy. Read More

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KDM5B promotes self-renewal of hepatocellular carcinoma cells through the microRNA-448-mediated YTHDF3/ITGA6 axis.

J Cell Mol Med 2021 Apr 7. Epub 2021 Apr 7.

Hainan General Hospital, Haikou, China.

Histone methylation plays important roles in mediating the onset and progression of various cancers, and lysine-specific demethylase 5B (KDM5B), as a histone demethylase, is reported to be an oncogene in hepatocellular carcinoma (HCC). However, the mechanism underlying its tumorigenesis remains undefined. Hence, we explored the regulatory role of KDM5B in HCC cells, aiming to identify novel therapeutic targets for HCC. Read More

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Posttranslational regulation of FOXA1 by Polycomb and BUB3/USP7 deubiquitin complex in prostate cancer.

Sci Adv 2021 Apr 7;7(15). Epub 2021 Apr 7.

Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Forkhead box protein A1 (FOXA1) is essential for androgen-dependent prostate cancer (PCa) growth. However, how FOXA1 levels are regulated remains elusive and its therapeutic targeting proven challenging. Here, we report FOXA1 as a nonhistone substrate of enhancer of zeste homolog 2 (EZH2), which methylates FOXA1 at lysine-295. Read More

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Distinct kinetic mechanisms of H3K4 methylation catalyzed by MLL3 and MLL4 core complexes.

J Biol Chem 2021 Apr 3:100635. Epub 2021 Apr 3.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB), Shanghai 200237, China. Electronic address:

The methyltransferases MLL3 and MLL4 primarily catalyze the mono-methylation of histone H3 lysine 4 (H3K4) on enhancers to regulate cell-type-specific gene expression and cell fate transition. MLL3 and MLL4 share almost identical binding partners and biochemical activities, but perform specific and non-redundant functions. The features and functions that distinguish MLL3 and MLL4 remain elusive. Read More

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The histone modification H3K4me3 is altered at the locus in Alzheimer's disease brain.

Future Sci OA 2021 Feb 9;7(4):FSO665. Epub 2021 Feb 9.

University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.

Several epigenome-wide association studies of DNA methylation have highlighted altered DNA methylation in the gene in Alzheimer's disease (AD) brain samples. However, no study has specifically examined histone modifications in the disease. We use chromatin immunoprecipitation-qPCR to quantify tri-methylation at histone 3 lysine 4 (H3K4me3) and 27 (H3K27me3) in the gene in entorhinal cortex from donors with high (n = 59) or low (n = 29) Alzheimer's disease pathology. Read More

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February 2021

Dopant-Dependent Toxicity of CeO Nanoparticles Is Associated with Dynamic Changes in H3K4me3 and H3K27me3 and Transcriptional Activation of NRF2 Gene in HaCaT Human Keratinocytes.

Int J Mol Sci 2021 Mar 17;22(6). Epub 2021 Mar 17.

Department of Biological Sciences, College of Natural Science, Inha University, 100 Inha-ro, Michuhol-gu, Incheon 22212, Korea.

Despite advances in the preparation of metal oxide (MO) nanoparticles (NPs) as catalysts for various applications, concerns about the biosafety of these particles remain. In this study, we prepared transition metal-doped cerium oxide (TM@CeO; TM = Cr, Mn, Fe, Co, or Ni) nanoparticles and investigated the mechanism underlying dopant-dependent toxicity in HaCaT human keratinocytes. We show that doping with Cr or Co but not Fe, Mn, or Ni increased the toxicity of CeO NPs in dose- and time-dependent manners and led to apoptotic cell death. Read More

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LSD1-BDNF activity in lateral hypothalamus-medial forebrain bundle area is essential for reward seeking behavior.

Prog Neurobiol 2021 Mar 30:102048. Epub 2021 Mar 30.

Department of Biotechnology, Savitribai Phule Pune University, Pune 411 007, India. Electronic address:

Reward induces activity-dependant gene expression and synaptic plasticity-related changes. Lysine-specific histone demethylase 1 (LSD1), a key enzyme driving histone modifications, regulates transcription in neural circuits of memory and emotional behavior. Herein, we focus on the role of LSD1 in modulating the expression of brain derived neurotrophic factor (BDNF), the master regulator of synaptic plasticity, in the lateral hypothalamus-medial forebrain bundle (LH-MFB) circuit during positive reinforcement. Read More

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A PRC2-independent function for EZH2 in regulating rRNA 2'-O methylation and IRES-dependent translation.

Nat Cell Biol 2021 Apr 1;23(4):341-354. Epub 2021 Apr 1.

Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Dysregulated translation is a common feature of cancer. Uncovering its governing factors and underlying mechanism are important for cancer therapy. Here, we report that enhancer of zeste homologue 2 (EZH2), previously known as a transcription repressor and lysine methyltransferase, can directly interact with fibrillarin (FBL) to exert its role in translational regulation. Read More

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DOT1L regulates thermogenic adipocyte differentiation and function via modulating H3K79 methylation.

Diabetes 2021 Apr 1. Epub 2021 Apr 1.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China, 201203

Brown and beige adipocytes are characterized as thermogenic adipocytes and have great potential for treating obesity and associated metabolic diseases. Here, we identify a conserved mammalian lysine 79 of histone H3 (H3K79) methyltransferase, disruptor of telomeric silencing -1 like (DOT1L), as a new epigenetic regulator that controls thermogenic adipocyte differentiation and function. We show that deletion of DOT1L in thermogenic adipocytes potently protects mice from diet-induced obesity, improves glucose homeostasis, alleviates hepatic steatosis, and facilitates adaptive thermogenesis Loss of DOT1L in primary preadipocytes significantly promotes brown and beige adipogenesis and thermogenesis Mechanistically, DOT1L epigenetically regulates the BAT-selective gene program through modulating H3K79 methylation, in particular H3K79me2 modification. Read More

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The Physcomitrella patens chromatin adaptor PpMRG1 interacts with H3K36me3 and regulates light-responsive alternative splicing.

Plant Physiol 2021 Apr;185(3):1229-1241

Institute of Plant and Microbial biology, Academia Sinica, Taipei, Taiwan.

Plants perceive dynamic light conditions and optimize their growth and development accordingly by regulating gene expression at multiple levels. Alternative splicing (AS), a widespread mechanism in eukaryotes that post-transcriptionally generates two or more messenger RNAs (mRNAs) from the same pre-mRNA, is rapidly controlled by light. However, a detailed mechanism of light-regulated AS is still not clear. Read More

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A novel proteomics approach to epigenetic profiling of circulating nucleosomes.

Sci Rep 2021 Mar 31;11(1):7256. Epub 2021 Mar 31.

Belgian Volition SRL, 22 Rue Phocas Lejeune, Parc Scientifique Crealys, 5032, Isnes, Belgium.

Alteration of epigenetic modifications plays an important role in human cancer. Notably, the dysregulation of histone post-translational modifications (PTMs) has been associated with several cancers including colorectal cancer (CRC). However, the signature of histone PTMs on circulating nucleosomes is still not well described. Read More

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[Role of histone demethylase KDM6B in HBx-mediated podocyte-macrophage transdifferentiation].

Zhonghua Yi Xue Za Zhi 2021 Mar;101(12):866-871

Department of Nephrology, the First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.

To explore the expression of lysine (k)-specific demethylase 6B (KDM6B) in the renal tissues of hepatitis B virus-associated glomerulonephritis (HBV-GN) patients and human podocytes transfected with hepatitis B virus X (HBx) gene, and its role in HBx-mediated podocyte-macrophage transdifferentiation (PMT). Forty-eight patients diagnosed as HBV-GN by renal biopsy from 2013 to 2018 at the Shanghai Jiaotong University Affiliated First People's Hospital were included in this study. Thirty patients with primary glomerulonephritis (PGN) and fifteen patients with renal tumor were chosen as control group. Read More

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Genome-wide analysis of long noncoding RNAs, 24-nt siRNAs, DNA methylation and H3K27me3 marks in Brassica rapa.

PLoS One 2021 31;16(3):e0242530. Epub 2021 Mar 31.

Institute of Scientific and Industrial Research, Osaka University, Mihogaoka, Ibaraki-city, Osaka, Japan.

Long noncoding RNAs (lncRNAs) are RNA fragments that generally do not code for a protein but are involved in epigenetic gene regulation. In this study, lncRNAs of Brassica rapa were classified into long intergenic noncoding RNAs, natural antisense RNAs, and intronic noncoding RNAs and their expression analyzed in relation to genome-wide 24-nt small interfering RNAs (siRNAs), DNA methylation, and histone H3 lysine 27 trimethylation marks (H3K27me3). More than 65% of the lncRNAs analyzed consisted of one exon, and more than 55% overlapped with inverted repeat regions (IRRs). Read More

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Androgens regulate ovarian gene expression by balancing Ezh2-Jmjd3 mediated H3K27me3 dynamics.

PLoS Genet 2021 Mar 30;17(3):e1009483. Epub 2021 Mar 30.

Reproductive and Developmental Sciences Program, Department of Animal Sciences, Michigan State University, East Lansing, MI, United States of America.

Conventionally viewed as male hormone, androgens play a critical role in female fertility. Although androgen receptors (AR) are transcription factors, to date very few direct transcriptional targets of ARs have been identified in the ovary. Using mouse models, this study provides three critical insights about androgen-induced gene regulation in the ovary and its impact on female fertility. Read More

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The CREB/KMT5A complex regulates PTP1B to modulate high glucose-induced endothelial inflammatory factor levels in diabetic nephropathy.

Cell Death Dis 2021 Mar 29;12(4):333. Epub 2021 Mar 29.

Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Diabetic nephropathy (DN) is the primary microvascular complication of diabetes mellitus and may result in end-stage renal disease. The overproduction of various inflammatory factors is involved in the pathogenesis of DN. Protein tyrosine phosphatase 1B (PTP1B) modulates the expression of a series of cytokines and nuclear factor kappa B (NF-κB) activity. Read More

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