1,593 results match your criteria h3k4 methylation

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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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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Epigenetic Characteristics of Human Subtelomeres Vary in Cells Utilizing the Alternative Lengthening of Telomeres (ALT) Pathway.

Life (Basel) 2021 Mar 26;11(4). Epub 2021 Mar 26.

Department of Genetics and Developmental Biology, Rappaport Faculty of Medicine and Research Institute, Technion, Haifa 31096, Israel.

Most human cancers circumvent senescence by activating a telomere length maintenance mechanism, most commonly involving telomerase activation. A minority of cancers utilize the recombination-based alternative lengthening of telomeres (ALT) pathway. The exact requirements for unleashing normally repressed recombination at telomeres are yet unclear. Read More

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Epigenetic Control of Infant B Cell Precursor Acute Lymphoblastic Leukemia.

Int J Mol Sci 2021 Mar 18;22(6). Epub 2021 Mar 18.

Lymphocyte Development and Disease Group, Josep Carreras Leukaemia Research Institute (IJC), Ctra. de Can Ruti, Camí de les Escoles s/n, 08916 Barcelona, Spain.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a highly aggressive malignancy, with poorer prognosis in infants than in adults. A genetic signature has been associated with this outcome but, remarkably, leukemogenesis is commonly triggered by genetic alterations of embryonic origin that involve the deregulation of chromatin remodelers. This review considers in depth how the alteration of epigenetic profiles (at DNA and histone levels) induces an aberrant phenotype in B lymphocyte progenitors by modulating the oncogenic drivers and tumor suppressors involved in key cancer hallmarks. Read More

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KDM5 inhibition offers a novel therapeutic strategy for the treatment of KMT2D mutant lymphomas.

Blood 2021 Mar 30. Epub 2021 Mar 30.

Queen Mary University of London, London, United Kingdom.

Loss-of-function mutations in KMT2D are a striking feature of the germinal centre (GC) lymphomas, resulting in decreased H3K4-methylation and altered gene expression. We hypothesised that inhibition of the KDM5 family, which demethylates H3K4me3/me2, would re-establish H3K4-methylation and restore the expression of genes repressed upon loss of KMT2D. KDM5-inhibition increased H3K4me3 levels and caused an anti-proliferative response in vitro, which was markedly greater in both endogenous and CRISPR-edited KMT2D mutant DLBCL cell lines, while tumour growth was inhibited in KMT2D mutant xenografts in vivo. Read More

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Inhibition of KDM1A activity restores adult neurogenesis and improves hippocampal memory in a mouse model of Kabuki syndrome.

Mol Ther Methods Clin Dev 2021 Mar 18;20:779-791. Epub 2021 Feb 18.

McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Kabuki syndrome (KS) is a rare cause of intellectual disability primarily caused by loss-of-function mutations in lysine-specific methyltransferase 2D (), which normally adds methyl marks to lysine 4 on histone 3. Previous studies have shown that a mouse model of KS ( ) demonstrates disruption of adult neurogenesis and hippocampal memory. Proof-of-principle studies have shown postnatal rescue of neurological dysfunction following treatments that promote chromatin opening; however, these strategies are non-specific and do not directly address the primary defect of histone methylation. Read More

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Design, Synthesis, and Evaluation of (2-Aminocyclopropyl)phenyl Derivatives as Novel Positron Emission Tomography Imaging Agents for Lysine-Specific Demethylase 1 in the Brain.

J Med Chem 2021 Apr 17;64(7):3780-3793. Epub 2021 Mar 17.

Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa 251-8555, Japan.

Dysregulation of histone H3 lysine 4 (H3K4) methylation is implicated in the pathogenesis of neurodevelopmental disorders. Lysine-specific demethylase 1 (LSD1) determines the methylation status of H3K4 through flavin adenine dinucleotide (FAD)-mediated histone demethylation. Therefore, LSD1 inhibition in the brain can be a novel therapeutic option for treating these disorders. Read More

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X chromosome escapee genes are involved in ischemic sexual dimorphism through epigenetic modification of inflammatory signals.

J Neuroinflammation 2021 Mar 12;18(1):70. Epub 2021 Mar 12.

Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX, 77030, USA.

Background: Stroke is a sexually dimorphic disease. Previous studies have found that young females are protected against ischemia compared to males, partially due to the protective effect of ovarian hormones, particularly estrogen (E). However, there are also genetic and epigenetic effects of X chromosome dosage that contribute to stroke sensitivity and neuroinflammation after injury, especially in the aged. Read More

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Vitamin C sensitizes triple negative breast cancer to PI3K inhibition therapy.

Theranostics 2021 20;11(8):3552-3564. Epub 2021 Jan 20.

John P. Hussman Institute for Human Genomics, Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida.

The clinical use of PI3K inhibitors, such as buparlisib, has been plagued with toxicity at effective doses. The aim of this study is to determine if vitamin C, a potent epigenetic regulator, can improve the therapeutic outcome and reduce the dose of buparlisib in treating -mutated triple negative breast cancer (TNBC). The response of TNBC cells to buparlisib was assessed by EC measurements, apoptosis assay, clonogenic assay, and xenograft assay in mice. Read More

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January 2021

KDM5C Expedites Lung Cancer Growth and Metastasis Through Epigenetic Regulation of MicroRNA-133a.

Onco Targets Ther 2021 22;14:1187-1204. Epub 2021 Feb 22.

Department of Thoracic Surgery, Zhengzhou Key Laboratory of Surgical Treatment for End-Stage Lung Diseases, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, People's Republic of China.

Background: KDM5C, a histone H3K4-specific demethylase, possess various biological functions in development of cancers. However, its relation to the microRNA (miRNA) regulation in lung cancer remains unknown. This study aims to study the regulatory role of KDM5C on modification of miR-133a in the progression of lung cancer. Read More

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February 2021

Long non-coding RNA ROR recruits histone transmethylase MLL1 to up-regulate TIMP3 expression and promote breast cancer progression.

J Transl Med 2021 03 2;19(1):95. Epub 2021 Mar 2.

Department of Pathology, Henan Provincial People's Hospital, No. 7, Weiwu Road, Zhengzhou, 450003, Henan, People's Republic of China.

Background: As a significant cause of cancer deaths worldwide, breast cancer continues to be a troublesome malignancy. Long non-coding RNAs (lncRNAs) have been implicated in the development of breast cancer. Abnormal methylation has been associated with unfavorable breast cancer prognosis. Read More

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Expression and Methylation of Histone 3 in Mice Chimeric Blastocysts.

Rep Biochem Mol Biol 2020 Oct;9(3):357-365

Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.

Background: Currently, the efficient production of chimeric mice and their survival are still challenging. Recent researches have indicated that preimplantation embryo culture media and manipulation lead to abnormal methylation of histone in the promotor region and consequently alter their gene expression pattern. This investigation was designed to evaluate the relationship between the methylation state of histone H3 and expression in mice chimeric blastocysts. Read More

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October 2020

SMYD3: a regulator of epigenetic and signaling pathways in cancer.

Clin Epigenetics 2021 Feb 26;13(1):45. Epub 2021 Feb 26.

Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, 41 Medlars Drive, Bethesda, MD, 20852, USA.

Chromatin modifiers and their implications in oncogenesis have been an exciting area of cancer research. These are enzymes that modify chromatin via post-translational modifications such as methylation, acetylation, sumoylation, phosphorylation, in addition to others. Depending on the modification, chromatin modifiers can either promote or repress transcription. Read More

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February 2021

A unique histone 3 lysine 14 chromatin signature underlies tissue-specific gene regulation.

Mol Cell 2021 Feb 17. Epub 2021 Feb 17.

Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden. Electronic address:

Organismal development and cell differentiation critically depend on chromatin state transitions. However, certain developmentally regulated genes lack histone 3 lysine 9 and 27 acetylation (H3K9ac and H3K27ac, respectively) and histone 3 lysine 4 (H3K4) methylation, histone modifications common to most active genes. Here we describe a chromatin state featuring unique histone 3 lysine 14 acetylation (H3K14ac) peaks in key tissue-specific genes in Drosophila and human cells. Read More

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February 2021

Role of CxxC-finger protein 1 in establishing mouse oocyte epigenetic landscapes.

Nucleic Acids Res 2021 03;49(5):2569-2582

Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.

During oogenesis, oocytes gain competence and subsequently undergo meiotic maturation and prepare for embryonic development; trimethylated histone H3 on lysine-4 (H3K4me3) mediates a wide range of nuclear events during these processes. Oocyte-specific knockout of CxxC-finger protein 1 (CXXC1, also known as CFP1) impairs H3K4me3 accumulation and causes changes in chromatin configurations. This study investigated the changes in genomic H3K4me3 landscapes in oocytes with Cxxc1 knockout and the effects on other epigenetic factors such as the DNA methylation, H3K27me3, H2AK119ub1 and H3K36me3. Read More

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Recognition of Histone H3 Methylation States by the PHD1 Domain of Histone Demethylase KDM5A.

ACS Chem Biol 2021 Feb 23. Epub 2021 Feb 23.

Department of Cellular and Molecular Pharmacology, University of California San Francisco, 600 16th Street, Genentech Hall, San Francisco, California 94158, United States.

PHD reader domains are chromatin binding modules often responsible for the recruitment of large protein complexes that contain histone modifying enzymes, chromatin remodelers, and DNA repair machinery. A majority of PHD domains recognize N-terminal residues of histone H3 and are sensitive to the methylation state of Lys4 in histone H3 (H3K4). Histone demethylase KDM5A, an epigenetic eraser enzyme that contains three PHD domains, is often overexpressed in various cancers, and its demethylation activity is allosterically enhanced when its PHD1 domain is bound to the H3 tail. Read More

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February 2021

Reversible Lysine Specific Demethylase 1 (LSD1) Inhibitors: A Promising Wrench to Impair LSD1.

J Med Chem 2021 Mar 23;64(5):2466-2488. Epub 2021 Feb 23.

Key Lab of Advanced Drug Preparation Technologies, Ministry of Education of China, State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Henan Province for Drug Quality and Evaluation, Institute of Drug Discovery and Development, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.

As a flavin adenine dinucleotide (FAD)-dependent monoamine oxidase, lysine specific demethylase 1 (LSD1/KDM1A) functions as a transcription coactivator or corepressor to regulate the methylation of histone 3 lysine 4 and 9 (H3K4/9), and it has emerged as a promising epigenetic target for anticancer treatment. To date, numerous inhibitors targeting LSD1 have been developed, some of which are undergoing clinical trials for cancer therapy. Although only two reversible LSD1 inhibitors CC-90011 and SP-2577 are in the clinical stage, the past decade has seen remarkable advances in the development of reversible LSD1 inhibitors. Read More

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Mechanisms of maternal intergenerational epigenetic inheritance.

Curr Opin Genet Dev 2021 Feb 16;67:151-162. Epub 2021 Feb 16.

Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Faculty of Sciences, University of Basel, 4056 Basel, Switzerland. Electronic address:

Mammalian embryos are formed by fusion of eggs and sperm. Here we provide an integrated overview of the major dynamic changes in transcriptional processes, chromatin composition and 3D organization which the maternal and paternal genomes undergo during oocyte and early embryonic development in mice. We derive mechanistic insights into molecular hierarchies and crosstalk between the various chromatin-associated processes that define three distinct types of maternal epigenetic memory states in oocytes to support pre-implantation and post-implantation development. Read More

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February 2021

Hippocampal epigenetic and insulin-like growth factor alterations in noninvasive versus invasive mechanical ventilation in preterm lambs.

Pediatr Res 2021 Feb 18. Epub 2021 Feb 18.

Department of Pediatrics, Division of Neonatology, School of Medicine, University of Utah, Salt Lake City, UT, 84132-2202, USA.

Background: The brain of chronically ventilated preterm human infants is vulnerable to collateral damage during invasive mechanical ventilation (IMV). Damage is manifest, in part, by learning and memory impairments, which are hippocampal functions. A molecular regulator of hippocampal development is insulin-like growth factor 1 (IGF1). Read More

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February 2021

Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer.

J Immunother Cancer 2021 Feb;9(2)

Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, China

Background: The activation of tumor-associated macrophages (TAMs) facilitates the progression of gastric cancer (GC). Cell metabolism reprogramming has been shown to play a vital role in the polarization of TAMs. However, the role of methionine metabolism in function of TAMs remains to be explored. Read More

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February 2021

Metformin Reduces Histone H3K4me3 at the Promoter Regions of Positive Cell Cycle Regulatory Genes in Lung Cancer Cells.

Cancers (Basel) 2021 Feb 10;13(4). Epub 2021 Feb 10.

Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.

This study aimed at understanding the effect of metformin on histone H3 methylation, DNA methylation, and chromatin accessibility in lung cancer cells. Metformin significantly reduced H3K4me3 level at the promoters of positive cell cycle regulatory genes such as CCNB2, CDK1, CDK6, and E2F8. Eighty-eight genes involved in cell cycle showed reduced H3K4me3 levels in response to metformin, and 27% of them showed mRNA downregulation. Read More

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February 2021

Acrylamide Induces Mitophagy and Alters Macrophage Phenotype via Reactive Oxygen Species Generation.

Int J Mol Sci 2021 Feb 8;22(4). Epub 2021 Feb 8.

Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

Acrylamide is a readily exposed toxic organic compound due to its formation in many carbohydrate rich foods that are cooked at high temperatures. Excessive production of reactive oxygen species (ROS), which is an important factor for mitophagy, has been reported to lead to airway inflammation, hyper-responsiveness, and remodeling. Epigenetic regulation is an important modification affecting gene transcription. Read More

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February 2021

The glucocorticoid receptor recruits the COMPASS complex to regulate inflammatory transcription at macrophage enhancers.

Cell Rep 2021 Feb;34(6):108742

Institute for Diabetes and Obesity (IDO) & Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich (HMGU) and German Center for Diabetes Research (DZD), 85764 Neuherberg (Munich), Germany; Metabolic Programming, School of Life Sciences Weihenstephan, ZIEL - Institute for Food & Health, Technische Universitaet Muenchen (TUM), 85354 Freising, Germany; Metabolic Biochemistry and Genetics, Gene Center, Ludwig-Maximilians-Universitaet LMU, 81377 Munich, Germany. Electronic address:

Glucocorticoids (GCs) are effective anti-inflammatory drugs; yet, their mechanisms of action are poorly understood. GCs bind to the glucocorticoid receptor (GR), a ligand-gated transcription factor controlling gene expression in numerous cell types. Here, we characterize GR's protein interactome and find the SETD1A (SET domain containing 1A)/COMPASS (complex of proteins associated with Set1) histone H3 lysine 4 (H3K4) methyltransferase complex highly enriched in activated mouse macrophages. Read More

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February 2021

SRF is a nonhistone methylation target of KDM2B and SET7 in the regulation of skeletal muscle differentiation.

Exp Mol Med 2021 Feb 9;53(2):250-263. Epub 2021 Feb 9.

Department of Pharmacology, Chonnam National University Medical School, Hwasun, Republic of Korea.

The demethylation of histone lysine residues, one of the most important modifications in transcriptional regulation, is associated with various physiological states. KDM2B is a demethylase of histones H3K4, H3K36, and H3K79 and is associated with the repression of transcription. Here, we present a novel mechanism by which KDM2B demethylates serum response factor (SRF) K165 to negatively regulate muscle differentiation, which is counteracted by the histone methyltransferase SET7. Read More

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February 2021

The COMPASS-like complex modulates fungal development and pathogenesis by regulating H3K4me3-mediated targeted gene expression in Magnaporthe oryzae.

Mol Plant Pathol 2021 Apr 8;22(4):422-439. Epub 2021 Feb 8.

Beijing Key Laboratory of New Technology in Agricultural Application, National Demonstration Center for Experimental Plant Production Education, Beijing University of Agriculture, Beijing, China.

Histone-3-lysine-4 (H3K4) methylation is catalysed by the multiprotein complex known as the Set1/COMPASS or MLL/COMPASS-like complex, an element that is highly evolutionarily conserved from yeast to humans. However, the components and mechanisms by which the COMPASS-like complex targets the H3K4 methylation of plant-pathogenic genes in fungi remain elusive. Here we present a comprehensive analysis combining biochemical, molecular, and genome-wide approaches to characterize the roles of the COMPASS-like family in the rice blast fungus Magnaporthe oryzae, a model plant pathogen. Read More

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Genome-Wide Identification and Characterization of Main Histone Modifications in Sorghum Decipher Regulatory Mechanisms Involved by mRNA and Long Noncoding RNA Genes.

J Agric Food Chem 2021 Feb 8;69(7):2337-2347. Epub 2021 Feb 8.

Institute for Interdisciplinary Research, Jianghan University, Wuhan 430056, China.

Post-translational modifications of histones play an important chromatic role of a transcript activity in eukaryotes. Even though mRNA and long noncoding RNA (lncRNA) genes share similar biogenetic processes, these transcript classes may differ in many ways. However, knowledge about the crosstalk between histone methylations and the two types of sorghum genes is still ambiguous. Read More

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February 2021

LncRNA LTSCCAT promotes tongue squamous cell carcinoma metastasis via targeting the miR-103a-2-5p/SMYD3/TWIST1 axis.

Cell Death Dis 2021 Feb 1;12(2):144. Epub 2021 Feb 1.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital, Guangzhou, China.

Abnormal expression of long-noncoding RNA is involved in the tumorigenesis and progression of various cancers, but the potential molecular regulatory mechanisms are unclear. Microbial flora and chronic inflammation, such as periodontitis, which is associated with oral cancer, affect the occurrence and progression of tumors. Accordingly, we stimulated the tongue squamous cell carcinoma (TSCC) cell lines CAL27 and SCC15 with a low concentration of lipopolysaccharide (LPS) from Porphyromonas gingivalis (P. Read More

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February 2021

Histone H3Q5 serotonylation stabilizes H3K4 methylation and potentiates its readout.

Proc Natl Acad Sci U S A 2021 Feb;118(6)

Ministry of Education Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;

Serotonylation of glutamine 5 on histone H3 (H3Q5ser) was recently identified as a permissive posttranslational modification that coexists with adjacent lysine 4 trimethylation (H3K4me3). While the resulting dual modification, H3K4me3Q5ser, is enriched at regions of active gene expression in serotonergic neurons, the molecular outcome underlying H3K4me3-H3Q5ser crosstalk remains largely unexplored. Herein, we examine the impact of H3Q5ser on the readers, writers, and erasers of H3K4me3. Read More

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February 2021

Loss of H3K27 methylation identifies poor outcomes in adult-onset acute leukemia.

Clin Epigenetics 2021 Jan 28;13(1):21. Epub 2021 Jan 28.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Acute leukemia is an epigenetically heterogeneous disease. The intensity of treatment is currently guided by cytogenetic and molecular genetic risk classifications; however these incompletely predict outcomes, requiring additional information for more accurate outcome predictions. We aimed to identify potential prognostic implications of epigenetic modification of histone proteins, with a focus on H3K4 and H3K27 methylation marks in relation to mutations in chromatin, splicing and transcriptional regulators in adult-onset acute lymphoblastic and myeloid leukemia. Read More

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January 2021

Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract.

Sci Rep 2021 Jan 26;11(1):2203. Epub 2021 Jan 26.

Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA.

S100A4, a member of the S100 family of multifunctional calcium-binding proteins, participates in several physiological and pathological processes. In this study, we demonstrate that S100A4 expression is robustly induced in differentiating fiber cells of the ocular lens and that S100A4 knockout mice develop late-onset cortical cataracts. Transcriptome profiling of lenses from S100A4 mice revealed a robust increase in the expression of multiple photoreceptor- and Müller glia-specific genes, as well as the olfactory sensory neuron-specific gene, S100A5. Read More

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January 2021