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Infect Drug Resist 2020 5;13:1307-1318. Epub 2020 May 5.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.

Objective: is a major diarrhoea-inducing pathogen in coastal areas. In this study, we analysed the pathogenic characteristics of and variation in isolated from acute diarrhoeal patients in seven hospitals in different areas of southeastern China from 2013 to 2017.

Methods: The fecal specimens of patients with acute diarrhoea were collected. Read More

Nature 2019 09 4;573(7773):281-286. Epub 2019 Sep 4.

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

Enzymes that catalyse CpG methylation in DNA, including the DNA methyltransferases 1 (DNMT1), 3A (DNMT3A) and 3B (DNMT3B), are indispensable for mammalian tissue development and homeostasis. They are also implicated in human developmental disorders and cancers, supporting the critical role of DNA methylation in the specification and maintenance of cell fate. Previous studies have suggested that post-translational modifications of histones are involved in specifying patterns of DNA methyltransferase localization and DNA methylation at promoters and actively transcribed gene bodies. Read More

J Proteomics 2019 09 5;208:103481. Epub 2019 Aug 5.

Proteomics Facility, Biochemical Sciences Division, CSIR-National Chemical Laboratory, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India. Electronic address:

Prediabetes is a risk factor for the development of diabetes. Early diagnosis of prediabetes may prevent the onset and progression of diabetes and its associated complications. Therefore, this study aimed at the identification of novel markers for efficient prediction of prediabetes. Read More

Ecotoxicol Environ Saf 2019 Mar 27;169:669-677. Epub 2018 Nov 27.

Departamento de Bioquímica, Centro de Biociências, Universidade Federal de Pernambuco, Pernambuco, Brazil. Electronic address:

The increase in urbanization and industrialization has contributed to the contamination of different environments by means of xenobiotic compounds, such as heavy metals, causing changes in microbial communities. Among these metals, the Mercury (Hg) is one the most prevalent toxic metals for the environment The present study aimed to evaluate the effect of mercury on the formation of biofilm by environmental (collected from urban stream water) and clinical isolates of Klebsiella pneumoniae. In addition, antibiotic resistance, virulence factors, and genetic diversity were investigated. Read More

Toxicol Lett 2018 Sep 16;293:45-50. Epub 2017 Nov 16.

Bundeswehr Institute of Pharmacology and Toxicology, 80937, Munich, Germany; Bundeswehr Medical Academy, Dept. Medical CBRN Defense, 80937, Munich, Germany. Electronic address:

The chemical warfare agent sulfur mustard (SM) can cause long-term health effects that may occur even years after a single exposure. The underlying pathophysiology is unknown, but epigenetic mechanisms are discussed as feasible explanation. "Epigenetics" depicts regulation of gene function without affecting the DNA sequence itself. Read More

EMBO Rep 2017 12 5;18(12):2131-2143. Epub 2017 Oct 5.

Institute of Health Sciences, Chinese Academy of Sciences-Jiaotong University School of Medicine, Shanghai, China

The histone H3 N-terminal protein domain (N-tail) is regulated by multiple posttranslational modifications, including methylation, acetylation, phosphorylation, and by proteolytic cleavage. However, the mechanism underlying H3 N-tail proteolytic cleavage is largely elusive. Here, we report that JMJD5, a Jumonji C (JmjC) domain-containing protein, is a Cathepsin L-type protease that mediates histone H3 N-tail proteolytic cleavage under stress conditions that cause a DNA damage response. Read More

Nucleic Acids Res 2017 Aug;45(14):8239-8254

Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo 0316, Norway.

Many cellular proteins are methylated on lysine residues and this has been most intensively studied for histone proteins. Lysine methylations on non-histone proteins are also frequent, but in most cases the functional significance of the methylation event, as well as the identity of the responsible lysine (K) specific methyltransferase (KMT), remain unknown. Several recently discovered KMTs belong to the so-called seven-β-strand (7BS) class of MTases and we have here investigated an uncharacterized human 7BS MTase currently annotated as part of the endothelin converting enzyme 2, but which should be considered a separate enzyme. Read More

Front Microbiol 2016 17;7:1864. Epub 2016 Nov 17.

Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of MedicineShanghai, China; Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of MedicineShanghai, China.

N-lysine acetylation is an abundant and important Post-translational modification in bacteria. We used the bacterial two-hybrid system to screen the genome library of the Typhimurium to identify potential proteins involved in acetyltransferase Pat - or deacetylase CobB-mediated acetylation. Then, the (de)acetylation assays were used to validate the potential targets, such as STM14_1074, NrdF, RhaR. Read More

PLoS Genet 2016 06 30;12(6):e1006146. Epub 2016 Jun 30.

Center for Genome Dynamics, The Jackson Laboratory, Bar Harbor, Maine, United States of America.

In many mammals, including humans and mice, the zinc finger histone methyltransferase PRDM9 performs the first step in meiotic recombination by specifying the locations of hotspots, the sites of genetic recombination. PRDM9 binds to DNA at hotspots through its zinc finger domain and activates recombination by trimethylating histone H3K4 on adjacent nucleosomes through its PR/SET domain. Recently, the isolated PR/SET domain of PRDM9 was shown capable of also trimethylating H3K36 in vitro, raising the question of whether this reaction occurs in vivo during meiosis, and if so, what its function might be. Read More

PLoS One 2015 14;10(9):e0136777. Epub 2015 Sep 14.

Department of Cosmeceutics, China Medical University, Taichung 404, Taiwan.

In our previous study, N-phenethyl caffeamide (K36) was proved to act as an antioxidant and an antiphotoaging agent by inhibiting type I procollagen degradation and stimulating collagen synthesis in human skin fibroblasts. In the present study, in vitro and in vivo experiments were conducted to investigate the mechanism of action and the antiinflammatory and antiphotoaging activity of K36. K36 reduced UVB-induced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthases (iNOS) expression by regulating IκB and p-IκB expression. Read More

Cell Struct Funct 2014 15;39(1):31-43. Epub 2014 Jan 15.

Department of Anatomy and Physiology, Faculty of Medicine, Saga University.

Multiple type I and II hair keratins are expressed in hair-forming cells but the role of each protein in hair fiber formation remains obscure. In this study, recombinant proteins of human type I hair keratins (K35, K36 and K38) and type II hair keratins (K81 and K85) were prepared using bacterial expression systems. The heterotypic subunit interactions between the type I and II hair keratins were characterized using two-dimensional gel electrophoresis and surface plasmon resonance (SPR). Read More

PLoS Genet 2011 Dec 29;7(12):e1002423. Epub 2011 Dec 29.

Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America.

Eukaryotic genomes are partitioned into active and inactive domains called euchromatin and heterochromatin, respectively. In Neurospora crassa, heterochromatin formation requires methylation of histone H3 at lysine 9 (H3K9) by the SET domain protein DIM-5. Heterochromatin protein 1 (HP1) reads this mark and directly recruits the DNA methyltransferase, DIM-2. Read More

PLoS One 2011 28;6(11):e28171. Epub 2011 Nov 28.

Genome Structure and Regulation, School of Biomedical Science and Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.

Hox genes play important roles in haematopoietic development in mammals. ASH1 is a member of the trithorax group (trxG) that is required for proper expression of Hox genes and is preferentially expressed in haematopoietic stem cells. We have recently reported that ASH1 methylates histone H3 at lysine 36 (K36) but its biological function has remained elusive. Read More

BMC Biochem 2011 Jul 4;12:34. Epub 2011 Jul 4.

Advanced Biomolecular Research Cluster, University of the Free State, Bloemfontein, South Africa.

Background: The involvement of histone acetylation in facilitating gene expression is well-established, particularly in the case of histones H3 and H4. It was previously shown in Saccharomyces cerevisiae that gene expression was significantly down-regulated and chromatin more condensed in stationary phase compared to exponential phase. We were therefore interested in establishing the acetylation state of histone H3 and H4 in stationary and in exponential phase, since the regulation of this modification could contribute to transcriptional shut-down and chromatin compaction during semi-quiescence. Read More

Cancer Prev Res (Phila) 2010 Oct 14;3(10):1292-302. Epub 2010 Sep 14.

Department of Oncology, Albert Einstein Cancer Center, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA.

The short-chain fatty acid sodium butyrate (NaB), produced in the colonic lumen, induces cell cycle arrest, differentiation, and/or apoptosis in colorectal carcinoma cells in vitro, establishing a potential role for NaB in colon cancer prevention. We have previously shown that butyrate decreases cyclin D1 and c-myc expression, each essential for intestinal tumor development, by transcriptional attenuation. Here, we determined that butyrate-induced transcriptional attenuation of the cyclin D1 and c-myc genes in SW837 human colorectal adenocarcinoma cells occurs at ∼100 nucleotides downstream of the transcription start site, with a similar positioning in Caco-2 cells. Read More

J Antimicrob Chemother 2010 May 7;65(5):986-90. Epub 2010 Mar 7.

Department of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu, Taiwan, ROC.

Objectives: Loss of outer membrane protein (Omp) is commonly encountered in multidrug-resistant Klebsiella pneumoniae. However, little is known about the association between Omp loss and virulence. In the present study, this association was investigated in K. Read More

J Mol Biol 2010 Jan 24;395(4):884-96. Epub 2009 Oct 24.

Institute of Pharmaceutical Chemistry/ZAFES, University of Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt, Germany.

5-Lipoxygenase (5-LO) gene expression is strongly upregulated during induction of myeloid cell differentiation by 1alpha,25-dihydroxyvitamin D(3) (calcitriol) and transforming growth factor-beta (TGFbeta) in a promoter-independent manner. In an activity-guided approach using reporter gene assays where the distal part of the 5-LO gene was included in the reporter gene plasmid, we localized vitamin D response elements (VDREs) within exon 10, exon 12, and intron M. We found that these newly identified VDRE sites are bound by vitamin D receptor both in vitro by gel-shift analysis and in vivo by chromatin immunoprecipitation assays. Read More

Mol Cell Biol 2009 Dec 12;29(24):6413-26. Epub 2009 Oct 12.

Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA 16802, USA.

Posttranslational modifications to histones have been studied extensively, but the requirement for the residues within the tails for different stages of transcription is less clear. Using RNR3 as a model, we found that the residues within the N terminus of H3 are predominantly required for steps after transcription initiation and chromatin remodeling. Specifically, deleting as few as 20 amino acids, or substituting glutamines for lysines in the tail, greatly impaired K36 methylation by Set2. Read More

Proc Natl Acad Sci U S A 2009 Apr 13;106(17):6956-61. Epub 2009 Apr 13.

Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, ON, Canada M5S 3E1.

Elongation by RNA polymerase II (RNAPII) is a finely regulated process in which many elongation factors contribute to gene regulation. Among these factors are the polymerase-associated factor (PAF) complex, which associates with RNAPII, and several cyclin-dependent kinases, including positive transcription elongation factor b (P-TEFb) in humans and BUR kinase (Bur1-Bur2) and C-terminal domain (CTD) kinase 1 (CTDK1) in Saccharomyces cerevisiae. An important target of P-TEFb and CTDK1, but not BUR kinase, is the CTD of the Rpb1 subunit of RNAPII. Read More

Int J Parasitol 2008 Aug 26;38(10):1083-97. Epub 2008 Jan 26.

Department of Entomology, The Pennsylvania State University, 501 ASI Building, University Park, PA 16802, USA.

Dynamic histone lysine methylation, regulated by methyltransferases and demethylases, plays fundamental roles in chromatin structure and gene expression in a wide range of eukaryotic organisms. A large number of SET-domain-containing proteins make up the histone lysine methyltransferase (HKMT) family, which catalyses the methylation of different lysine residues with relatively high substrate specificities. Another large family of Jumonji C (JmjC)-domain-containing histone lysine demethylases (JHDMs) reverses histone lysine methylation with both lysine site and methyl-state specificities. Read More

Proc Natl Acad Sci U S A 2007 Nov 14;104(47):18439-44. Epub 2007 Nov 14.

Nuclear Receptor Biology Section, Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Covalent modifications of histones, such as acetylation and methylation, play important roles in the regulation of gene expression. Histone lysine methylation has been implicated in both gene activation and repression, depending on the specific lysine (K) residue that becomes methylated and the state of methylation (mono-, di-, or trimethylation). Methylation on K4, K9, and K36 of histone H3 has been shown to be reversible and can be removed by site-specific demethylases. Read More

Biochem Biophys Res Commun 2008 Jan 5;365(3):589-94. Epub 2007 Nov 5.

Genome Structure and Expression, School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo 113-8610, Japan.

We have previously isolated a mammalian homologue of Drosophila discsabsent, small, orhomeotic-1 (ash1) from the murine thymus, and recently shown that its SET domain methylates histone H3 lysine 36 (K36). Expression of ASH1 has been reported to be increased in NOD thymocytes in a BDC2.5 clonotype background, but its function in T cell development has remained elusive. Read More

Gene 2007 Aug 1;397(1-2):161-8. Epub 2007 May 1.

Genome Structure and Expression, School of Biomedical Science, and Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, Japan.

Drosophila discs absent, small, or homeotic-1 (ASH1) is a member of trithorax-group proteins that play essential roles in epigenetic regulation of Hox genes. Drosophila ASH1 genetically interacts with trithorax and has been reported to methylate histone H3 lysine 4 (K4) as well as H3 K9 and H4 K20. The function of mammalian ASH1, by contrast, has remained largely unknown. Read More

Cell 2006 Sep;126(5):905-16

Gurdon Institute and Department of Pathology, Tennis Court Road, Cambridge, CB2 1QR, UK.

The cis-trans isomerization of proline serves as a regulatory switch in signaling pathways. We identify the proline isomerase Fpr4, a member of the FK506 binding protein family in Saccharomyces cerevisiae, as an enzyme which binds the amino-terminal tail of histones H3 and H4 and catalyses the isomerization of H3 proline P30 and P38 in vitro. We show that P38 is necessary for methylation of K36 and that isomerization by Fpr4 inhibits the ability of Set2 to methylate H3 K36 in vitro. Read More

Eukaryot Cell 2005 Aug;4(8):1455-64

Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, USA.

The SET domain is an evolutionarily conserved domain found predominantly in histone methyltransferases (HMTs). The Neurospora crassa genome includes nine SET domain genes (set-1 through set-9) in addition to dim-5, which encodes a histone H3 lysine 9 HMT required for DNA methylation. We demonstrate that Neurospora set-2 encodes a histone H3 lysine 36 (K36) methyltransferase and that it is essential for normal growth and development. Read More

Int J Cancer 2004 Mar;109(1):24-37

Department of Microbiology, Faculty of Medicine, National University of Singapore, Kent Ridge, Singapore.

We previously reported that messenger RNA expression of DENN (differentially expressed in normal and neoplastic cells) is considerably higher in cancer cell lines than in normal cells. In our present study, we established that certain cancer cell lines express conspicuously higher levels of the 2 DENN isoforms in contrast to the 2 pro-apoptotic IG20 isoforms. Antisense DENN oligodeoxynucleotide treatment of K36 cells in vitro induced extensive apoptosis, while antisense DENN silencing of K36 tumor-bearing mice caused significant tumor regression in vivo. Read More

Cell Immunol 1995 Nov;166(1):141-53

Laboratory of Molecular Immunology, National University of Singapore.

The introduction and expression of allogeneic MHC class I genes in tumors can generate tumor-specific immunity which subsequently results in the regression of parental tumors. Immunization of naive (AKR/J x C57BL/6)F1 mice with H-2Kb-transformed K36 tumor cells was found to render recipient mice immune to a subsequent challenge by parental K36 tumor cells. Two types of cytotoxic T effector cells were demonstrated in these immune mice. Read More

Int J Cancer 1994 Apr;57(2):216-23

Laboratory of Molecular Immunology, National University of Singapore.

We have employed the DNA-mediated gene transfer method to introduce the allogenic major-histocompatibility-complex(MHC)-class-I gene H-2Kb into the K36.16 tumor cells, H-2k, in order to generate tumor-specific immunity. The acquisition of immunogenicity by the H-2Kb-transformed clones following gene transfer is associated with the reduction of constitutive reactive superoxide radicals. Read More

Mol Biol (Mosk) 1990 Jul-Aug;24(4):968-76

Genes encoding virus-specific late proteins with molecular mass 36 kDa and 12 kDa were mapped in HindIII-P DNA fragment of vaccinia virus strain L-IVP by hybrid selection of RNA to cloned DNA fragments followed by in vitro translation. RNA origin site of the 36K protein was detected in HindIII-J fragment. Nucleotide sequences of these genes were determined. Read More

Nature 1984 Oct 25-31;311(5988):750-2

Major histocompatibility complex (MHC) class I molecules can function as specific target antigens in T-cell-mediated cytotoxity. In addition, T cells can kill target cells through non-MHC antigens, for example, virally infected cells, if the target and effector cells express the same MHC class I antigens. Consequently, quantitative and/or qualitative variations in the expression of the H-2/HLA antigens on the target cells could interfere with MHC-restricted immune reactions. Read More