DOCSLIB.ORG

Genome-Wide Regulation of Cpg Methylation by Eccebpα in Acute Myeloid Leukemia [Version 1; Peer Review: 1 Approved, 1 Approved with Reservations]

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Genome-Wide Regulation of Cpg Methylation by Eccebpα in Acute Myeloid Leukemia [Version 1; Peer Review: 1 Approved, 1 Approved with Reservations] F1000Research 2021, 10:204 Last updated: 31 AUG 2021 RESEARCH ARTICLE Genome-wide regulation of CpG methylation by ecCEBPα in acute myeloid leukemia [version 1; peer review: 1 approved, 1 approved with reservations] Adewale J. Ogunleye 1, Ekaterina Romanova2, Yulia A. Medvedeva1,2 1Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, Moscow, Russian Federation 2Research Center of Biotechnology, Institute of Bioengineering, Russian Academy of Sciences, Moscow, Russian Federation v1 First published: 11 Mar 2021, 10:204 Open Peer Review https://doi.org/10.12688/f1000research.28146.1 Latest published: 31 Aug 2021, 10:204 https://doi.org/10.12688/f1000research.28146.2 Reviewer Status Invited Reviewers Abstract Background: Acute myeloid leukemia (AML) is a hematopoietic 1 2 malignancy characterized by genetic and epigenetic aberrations that alter the differentiation capacity of myeloid progenitor cells. The version 2 transcription factor CEBPα is frequently mutated in AML patients (revision) leading to an increase in DNA methylation in many genomic locations. 31 Aug 2021 Previously, it has been shown that ecCEBPα (extra coding CEBPα) - a lncRNA transcribed in the same direction as CEBPα gene - regulates version 1 DNA methylation of CEBPα promoter in cis. Here, we hypothesize that 11 Mar 2021 report report ecCEBPα could participate in the regulation of DNA methylation in trans. 1. Amrita Singh , CSIR Institute of Genomics Method: First, we retrieved the methylation profile of AML patients with mutated CEBPα locus from The Cancer Genome Atlas (TCGA). We and Integrative Biology (CSIR-IGIB), New then predicted the ecCEBPα secondary structure in order to check the Delhi, India potential of ecCEBPα to form triplexes around CpG loci and checked if triplex formation influenced CpG methylation, genome-wide. 2. Oleg N. Demidov , University of Results: Using DNA methylation profiles of AML patients with a Bourgogne-Franche Comté, Dijon, France mutated CEBPα locus, we show that ecCEBPα could interact with DNA by forming DNA:RNA triple helices and protect regions near its Any reports and responses or comments on the binding sites from global DNA methylation. Further analysis revealed article can be found at the end of the article. that triplex-forming oligonucleotides in ecCEBPα are structurally unpaired supporting the DNA-binding potential of these regions. ecCEBPα triplexes supported with the RNA-chromatin co-localization data are located in the promoters of leukemia-linked transcriptional factors such as MLF2. Discussion: Overall, these results suggest a novel regulatory mechanism for ecCEBPα as a genome-wide epigenetic modulator through triple-helix formation which may provide a foundation for sequence-specific engineering of RNA for regulating methylation of specific genes. Page 1 of 15 F1000Research 2021, 10:204 Last updated: 31 AUG 2021 Keywords Acute myeloid leukemia, Triplex, DNA methylation, long non coding RNA, extra-coding CEBPα Corresponding author: Adewale J. Ogunleye ([email protected]) Author roles: Ogunleye AJ: Formal Analysis, Investigation, Methodology, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing; Romanova E: Conceptualization, Data Curation, Supervision; Medvedeva YA: Conceptualization, Funding Acquisition, Methodology, Resources, Software, Supervision, Validation, Visualization, Writing – Review & Editing Competing interests: No competing interests were disclosed. Grant information: The work has been partially supported by Russian Science Foundation (grant 18-14-00240) to YAM and the Ministry of the Sciences and Higher Education of the Russian Federation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2021 Ogunleye AJ et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite this article: Ogunleye AJ, Romanova E and Medvedeva YA. Genome-wide regulation of CpG methylation by ecCEBPα in acute myeloid leukemia [version 1; peer review: 1 approved, 1 approved with reservations] F1000Research 2021, 10:204 https://doi.org/10.12688/f1000research.28146.1 First published: 11 Mar 2021, 10:204 https://doi.org/10.12688/f1000research.28146.1 Page 2 of 15 F1000Research 2021, 10:204 Last updated: 31 AUG 2021 Introduction granulocyte differentiation20. Mechanistic studies via reduced Acute myeloid leukemia (AML) is a malignant tumor charac- representation bisulfite sequencing and RNA immunoprecipita- terized by the proliferation of undifferentiated myeloblasts1,2. tion sequencing shows that ecCEBPα suppresses DNA meth- It is the most prevalent form of leukemia in older adults ylation in cis- by acting as a shield that sequesters DNMT1 (>60 years) with an annual mortality rate of 50% and a 5-year from the CEBPα promoter. We speculate that ecCEBPα could survival rate of 24%2,3. With the combined effects of the global regulate DNMT1 activities in distant DNA regions (in trans-) increase in average life expectancy and AML drug inefficiency, as well. The mechanism of this potential interaction is to be the number of patients is expected to significantly increase determined. in the coming years4,5. Methods The current understanding of the molecular interplay in AML ecCEBPα sequence has been defined under two distinct categories; (i) genetic In the recent version of GENCODE, ecCEBPα is not anno- abnormalities and (ii) non-random chromosomal rearrangements. tated most likely due to an overlap with a protein-coding gene Cases of AML with chromosomal rearrangements as t(15;17) CEBPα on the same strand. We retrieved the complete ecCEBPα [PML-RARA], t(9;22) [BCR-ABL], inv(16) [CBFB-MYH11], sequence from the human genome (hg19, chr19: 33298573- t(8;21) [RUNX1-ETO] are called cytogenetically abnormal 33303358) based on information reported in the work of (CA-AML), while cases with genetic abnormalities (including Di Ruscio et al.20. ecCEBPα is approximately 4.8kb and it over- frequent mutations in DNMT3A, NPM1, CEBPα, IDH1/2, TET2, laps with the intronless CEBPα gene (~2.6kb) on the same FLT3-ITD) are called cytogenetically normal (CN-AML)1,4. strand. ecCEBPα does not share either the same transcription The former accounts for 50–55%, while the latter accounts for start site (TSS) or transcription end site (TES) with CEBPα, start- 45–50% of diagnosed AML cases6,7. Even though these muta- ing ~0.89kb upstream and ending ~1.46kb downstream of the tions and chromosomal alterations are crucial for initiating CEBPα gene. AML, they are not sufficient to explain AML progression, 8 heterogeneity, and relapse . DNA methylation data processing CpG methylation (Illumina 450K array) and CEBPα muta- Recently, studies have identified the role of non-coding tion data for 186 AML patients were retrieved from the Cancer RNAs, especially long non-coding RNAs (lncRNA) in the ini- Genome Atlas (TCGA: http://firebrowse.org). CpG methyla- tiation and progression of cancers9–11. LncRNAs are emerging tion levels were measured in 307796 unique loci. We split all the functional transcriptional products of at least 200 nucleotides AML patients into two groups based on CEBPα mutation status lacking an open reading frame. Although they account for a (13 patients with a CEBPα mutation and 173 patients without a large proportion of transcriptional products in mammals (about mutation). We classified a CpG position as hypermethylated 58,000 loci)12, only a small number of lncRNAs have been (HM) in patients with a CEBPα locus mutation if DNA meth- well characterized. Although lncRNAs are mostly not con- ylation level was significantly increased in the case of a served evolutionarily, they are heavily regulated suggesting their CEBPα mutation (t-test, FDR ≤0.05 and Δ-value ≥0.1) and all functional role12,13. They may function either as signal trans- non-hypermethylated (NHM) CpG in the case of a CEBPα ducers, protein guides, or molecular scaffolds to regulate mutation were classified as non-hypermethylated CpGs (t-test, transcriptional and epigenetic events14–16. Some lncRNAs per- FDR >0.05 and |Δ-value| <0.1). As a result, we obtained 11955 form these functions in cis- by modulating transcription of HM and 261433 NHM CpGs. nearby genes (Dum)17 or act in trans-, by modulating genes 18 at multiple distant loci (MALAT1) , while some can do both Secondary structure and triplex prediction (HOTAIR)9,19. As suggested in a previous study22, unpaired RNA nucleotides are more likely to form triplexes with DNA. We predicted Recent studies have identified lncRNAs for their remark- RNA secondary structure using RNAplfold (V 2.4.14), from able role in regulating major epigenetic processes such as DNA the Vienna suite using a cut-off for pairing probability (-c) of methylation and chromatin remodeling. DNA methylation in 0.123,24. To search for potential interactions between ecCEBPα mammals is coordinated by one of the three DNA methyl- and DNA target regions we used only unpaired nucleotides, transferases (DNMT); DNMT1, DNMT3A, and DNMT3B7,17,20. while the nucleotides predicted to pair were replaced with ‘N’. LncRNAs have been identified in recent studies as important agents that can modulate DNA methylation, either by activating or DNA target regions were defined as 100 nucleotides centered at repressing DNMTs. For example, the
Load more

Recommended publications
  • Mclean, Chelsea.Pdf
    COMPUTATIONAL PREDICTION AND EXPERIMENTAL VALIDATION OF NOVEL MOUSE IMPRINTED GENES A Dissertation Presented to the Faculty of the Graduate School of Cornell University In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy by Chelsea Marie McLean August 2009 © 2009 Chelsea Marie McLean COMPUTATIONAL PREDICTION AND EXPERIMENTAL VALIDATION OF NOVEL MOUSE IMPRINTED GENES Chelsea Marie McLean, Ph.D. Cornell University 2009 Epigenetic modifications, including DNA methylation and covalent modifications to histone tails, are major contributors to the regulation of gene expression. These changes are reversible, yet can be stably inherited, and may last for multiple generations without change to the underlying DNA sequence. Genomic imprinting results in expression from one of the two parental alleles and is one example of epigenetic control of gene expression. So far, 60 to 100 imprinted genes have been identified in the human and mouse genomes, respectively. Identification of additional imprinted genes has become increasingly important with the realization that imprinting defects are associated with complex disorders ranging from obesity to diabetes and behavioral disorders. Despite the importance imprinted genes play in human health, few studies have undertaken genome-wide searches for new imprinted genes. These have used empirical approaches, with some success. However, computational prediction of novel imprinted genes has recently come to the forefront. I have developed generalized linear models using data on a variety of sequence and epigenetic features within a training set of known imprinted genes. The resulting models were used to predict novel imprinted genes in the mouse genome. After imposing a stringency threshold, I compiled an initial candidate list of 155 genes.
    [Show full text]
  • Use Tumor Suppressor Genes As Biomarkers for Diagnosis Of
    www.nature.com/scientificreports OPEN Use tumor suppressor genes as biomarkers for diagnosis of non‑small cell lung cancer Chuantao Zhang1,3, Man Jiang1,3, Na Zhou1, Helei Hou1, Tianjun Li1, Hongsheng Yu1, Yuan‑De Tan2* & Xiaochun Zhang1* Lung cancer is the leading cause of death worldwide. Especially, non‑small cell lung cancer (NSCLC) has higher mortality rate than the other cancers. The high mortality rate is partially due to lack of efcient biomarkers for detection, diagnosis and prognosis. To fnd high efcient biomarkers for clinical diagnosis of NSCLC patients, we used gene diferential expression and gene ontology (GO) to defne a set of 26 tumor suppressor (TS) genes. The 26 TS genes were down‑expressed in tumor samples in cohorts GSE18842, GSE40419, and GSE21933 and at stages 2 and 3 in GSE19804, and 15 TS genes were signifcantly down‑expressed in tumor samples of stage 1. We used S‑scores and N‑scores defned in correlation networks to evaluate positive and negative infuences of these 26 TS genes on expression of other functional genes in the four independent cohorts and found that SASH1, STARD13, CBFA2T3 and RECK were strong TS genes that have strong accordant/discordant efects and network efects globally impacting the other genes in expression and hence can be used as specifc biomarkers for diagnosis of NSCLC cancer. Weak TS genes EXT1, PTCH1, KLK10 and APC that are associated with a few genes in function or work in a special pathway were not detected to be diferentially expressed and had very small S‑scores and N‑scores in all collected datasets and can be used as sensitive biomarkers for diagnosis of early cancer.
    [Show full text]
  • Genetic Investigation in Non-Obstructive Azoospermia: from the X Chromosome to The
    DOTTORATO DI RICERCA IN SCIENZE BIOMEDICHE CICLO XXIX COORDINATORE Prof. Persio dello Sbarba Genetic investigation in non-obstructive azoospermia: from the X chromosome to the whole exome Settore Scientifico Disciplinare MED/13 Dottorando Tutore Dott. Antoni Riera-Escamilla Prof. Csilla Gabriella Krausz _______________________________ _____________________________ (firma) (firma) Coordinatore Prof. Carlo Maria Rotella _______________________________ (firma) Anni 2014/2016 A la meva família Agraïments El resultat d’aquesta tesis és fruit d’un esforç i treball continu però no hauria estat el mateix sense la col·laboració i l’ajuda de molta gent. Segurament em deixaré molta gent a qui donar les gràcies però aquest són els que em venen a la ment ara mateix. En primer lloc voldria agrair a la Dra. Csilla Krausz por haberme acogido con los brazos abiertos desde el primer día que llegué a Florencia, por enseñarme, por su incansable ayuda y por contagiarme de esta pasión por la investigación que nunca se le apaga. Voldria agrair també al Dr. Rafael Oliva per haver fet possible el REPROTRAIN, per haver-me ensenyat moltíssim durant l’època del màster i per acceptar revisar aquesta tesis. Alhora voldria agrair a la Dra. Willy Baarends, thank you for your priceless help and for reviewing this thesis. També voldria donar les gràcies a la Dra. Elisabet Ars per acollir-me al seu laboratori a Barcelona, per ajudar-me sempre que en tot el què li he demanat i fer-me tocar de peus a terra. Ringrazio a tutto il gruppo di Firenze, che dal primo giorno mi sono trovato come a casa.
    [Show full text]
  • Switching Roles for DNA and Histone Methylation Depend on Evolutionary Ages of Human Endogenous Retroviruses
    Downloaded from genome.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press Research Switching roles for DNA and histone methylation depend on evolutionary ages of human endogenous retroviruses Hitoshi Ohtani,1,3 Minmin Liu,1,3 Wanding Zhou,1 Gangning Liang,2 and Peter A. Jones1 1Van Andel Research Institute, Grand Rapids, Michigan 49503, USA; 2Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA We provide a comprehensive genomic and epigenomic map of the more than 500,000 endogenous retroviruses (ERVs) and fragments that populate the intergenic regions of the human genome. The repressive epigenetic marks associated with the ERVs, particularly long terminal repeats (LTRs), show a remarkable switch in silencing mechanisms, depending on the evo- lutionary age of the LTRs. Young LTRs tend to be CpG rich and are mainly suppressed by DNA methylation, whereas intermediate age LTRs are associated predominantly with histone modifications, particularly histone H3 lysine 9 (H3K9) methylation. Young LTRs can be reactivated by treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine (5-aza-CdR) alone, but their level of expression is much increased by 5-aza-CdR treatment plus knockdown of one of several H3K9 methyltransferases or of the H3K27 methyltransferase EZH2. The removal of cytosine methylation led to rapid, widespread increases in H3K9me3 in the LTRs. Intermediate age LTRs had lower CpG densities and were not up-regulated by 5-aza-CdR treatment, but they were sensitive to knockdown of H3K9 methyltransferases. Unlike the situation in embry- onic stem cells, the polycomb repressive complex (PRC2) has a minor role in LTR suppression by itself and is only a player after removal of cytosine methylation in the analyzed cancer cell line.
    [Show full text]
  • Suv39h-Catalysed H3k9me3 Is Critical for Euchromatic Genome Organisation and the Maintenance of Gene Transcription
    bioRxiv preprint doi: https://doi.org/10.1101/2020.08.13.249078; this version posted August 14, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Suv39h-catalysed H3K9me3 is critical for euchromatic genome organisation and the maintenance of gene transcription Christine R. Keenan1,2,4*, Hannah D. Coughlan1,2,4, Nadia Iannarella1, Timothy M. Johanson1,2, Wing Fuk Chan1,2, Alexandra L. Garnham1,2, Gordon K. Smyth1,3,5, Rhys S. Allan1,2,5* Affiliations: 1The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia. 2DePartment of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010, Australia. 3School of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria, 3010, Australia. 4,5These authors contributed equally *Corresponding authors: Christine R. Keenan ([email protected]) and Rhys S. Allan ([email protected]). Immunology Division, Walter and Eliza Hall Institute of Medical Research 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.13.249078; this version posted August 14, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Summary H3K9me3-dependent heterochromatin is critical for the silencing of repeat-rich Pericentromeric regions and also has key roles in repressing lineage-inaPProPriate Protein-coding genes in differentiation and develoPment. Here, we investigate the molecular consequences of heterochromatin loss in cells deficient in both Suv39h1 and Suv39h2 (Suv39DKO), the major mammalian histone methyltransferase enzymes that catalyse heterochromatic H3K9me3 dePosition.
    [Show full text]
  • The Emerging Role of Lysine Methyltransferase SETD8 in Human
    Milite et al. Clinical Epigenetics (2016) 8:102 DOI 10.1186/s13148-016-0268-4 REVIEW Open Access The emerging role of lysine methyltransferase SETD8 in human diseases Ciro Milite1,2, Alessandra Feoli1,2,3, Monica Viviano1,2, Donatella Rescigno1,2,3, Agostino Cianciulli1,2,3, Amodio Luca Balzano1,2,3, Antonello Mai4, Sabrina Castellano1,2,5 and Gianluca Sbardella1,2* Abstract SETD8/SET8/Pr-SET7/KMT5A is the only known lysine methyltransferase (KMT) that monomethylates lysine 20 of histone H4 (H4K20) in vivo. Lysine residues of non-histone proteins including proliferating cell nuclear antigen (PCNA) and p53 are also monomethylated. As a consequence, the methyltransferase activity of the enzyme is implicated in many essential cellular processes including DNA replication, DNA damage response, transcription modulation, and cell cycle regulation. This review aims to provide an overview of the roles of SETD8 in physiological and pathological pathways and to discuss the progress made to date in inhibiting the activity of SETD8 by small molecules, with an emphasis on their discovery, selectivity over other methyltransferases and cellular activity. Background side chain of a particular lysine residue [9]. Most KMTs Lysine methylation on histone tails is a prevalent post- contain the SET (Su(var), Enhancer of zeste, Trithorax) translational modification and, together with arginine domain and are thought to catalyze a sequential bi-bi methylation, plays a primary role in the regulation of kinetic mechanism in which both substrate association chromatin structure and gene transcription, both in and product release occur in a random manner [9]. Yet, physiological and pathological conditions [1–5].
    [Show full text]
  • Genome-Wide Analysis of Epigenetics and Alternative Promoters in Cancer Cells
    GENOME-WIDE ANALYSIS OF EPIGENETICS AND ALTERNATIVE PROMOTERS IN CANCER CELLS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Jiejun Wu, M.D. & M.S. ***** The Ohio State University 2007 Dissertation Committee: Approved by: Dr. Christoph Plass, Adviser Dr. Tim H.-M. Huang, Adviser ____________________________________ Dr. Donald Harry Dean Adviser Graduate Program in Molecular Genetics Dr. Amanda Simcox Dr. Huey-Jen Lin ABSTRACT Genome-wide approaches, such as ChIP-chip, have been widely applied to explore the patterns of epigenetic markers and the interactions between DNA and proteins. Compared to candidate gene studies, the application of epigenomic and genomic tools in these fields provides more comprehensive understanding of normal and abnormal events in cells, such as those biological changes promoting cancer development. In the first part, I studied the relations between two well-known epigenetic markers, DNA methylation and histone modifications. Previous studies of individual genes have shown that in a self-enforcing way, dimethylation at histone 3 lysine 9 (dimethyl-H3K9) and DNA methylation cooperate to maintain a repressive mode of inactive genes. Less clear is whether this cooperation is generalized in mammalian genomes, such as the mouse genome. Here I use epigenomic tools to simultaneously interrogate chromatin modifications and DNA methylation in a mouse leukemia cell line, L1210. Histone modifications on H3K9 and DNA methylation in L1210 were profiled by both global CpG island array and custom mouse promoter array analysis. I used chromatin immunoprecipitation microarray (ChIP-chip) to examine acetyl-H3K9 and dimethyl-H3K9.
    [Show full text]
  • Consensuspathdb: Toward a More Complete Picture of Cell Biology Atanas Kamburov*, Konstantin Pentchev, Hanna Galicka, Christoph Wierling, Hans Lehrach and Ralf Herwig
    D712–D717 Nucleic Acids Research, 2011, Vol. 39, Database issue Published online 11 November 2010 doi:10.1093/nar/gkq1156 ConsensusPathDB: toward a more complete picture of cell biology Atanas Kamburov*, Konstantin Pentchev, Hanna Galicka, Christoph Wierling, Hans Lehrach and Ralf Herwig Vertebrate Genomics Department, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195 Berlin, Germany Received October 15, 2010; Revised October 18, 2010; Accepted October 27, 2010 ABSTRACT while others focus on the curation of biochemical ConsensusPathDB is a meta-database that inte- pathways and still others on gene regulatory interactions. grates different types of functional interactions In the cell, however, all different types of functional inter- actions are operative at the same time: to give an example from heterogeneous interaction data resources. scenario, genes are regulated to produce proteins that Physical protein interactions, metabolic and sig- interact physically with other proteins to form complexes naling reactions and gene regulatory interactions that catalyze metabolic reactions. ConsensusPathDB, are integrated in a seamless functional association which we previously reported in (3), assembles a func- network that simultaneously describes multiple tional association network from multiple heterogeneous functional aspects of genes, proteins, complexes, public interaction resources by integrating physical metabolites, etc. With 155 432 human, 194 480 entities based on their accession numbers and functional yeast and 13 648 mouse complex functional inter- interactions based on their participants. As the combined actions (originating from 18 databases on human interaction network in ConsensusPathDB reveals multiple and eight databases on yeast and mouse inter- functional aspects of cellular entities at the same time actions each), ConsensusPathDB currently consti- by combining highly complementary data, it is closer to biological reality than the separate source networks.
    [Show full text]
  • Comparative Mapping of Human Chromosome 10 to Pig Chromosomes 10 and 14*
    SHORT COMMUNICATION doi:10.1111/j.1365-2052.2004.01165.x Comparative mapping of human chromosome 10 to pig chromosomes 10 and 14* D. Nonneman and G. A. Rohrer USDA, ARS, US Meat Animal Research Center, Clay Center, NE, USA Summary Identification of predictive markers in QTL regions that impact production traits in com- mercial populations of swine is dependent on construction of dense comparative maps with human and mouse genomes. Chromosomal painting in swine suggests that large genomic blocks are conserved between pig and human, while mapping of individual genes reveals that gene order can be quite divergent. High-resolution comparative maps in regions affecting traits of interest are necessary for selection of positional candidate genes to evaluate nucleotide variation causing phenotypic differences. The objective of this study was to construct an ordered comparative map of human chromosome 10 and pig chro- mosomes 10 and 14. As a large portion of both pig chromosomes are represented by HSA10, genes at regularly spaced intervals along this chromosome were targeted for placement in the porcine genome. A total of 29 genes from human chromosome 10 were mapped to porcine chromosomes 10 (SSC10) and 14 (SSC14) averaging about 5 Mb dis- tance of human DNA per marker. Eighteen genes were assigned by linkage in the MARC mapping population, five genes were physically assigned with the IMpRH mapping panel and seven genes were assigned on both maps. Seventeen genes from human 10p mapped to SSC10, and 12 genes from human 10q mapped to SSC14. Comparative maps of mam- malian species indicate that chromosomal segments are conserved across several species and represent syntenic blocks with distinct breakpoints.
    [Show full text]
  • Prognostic Significance of Epigenetic Regulatory Gene Expression in Patients with Non-Small-Cell Lung Cancer
    www.aging-us.com AGING 2021, Vol. 13, No. 5 Research Paper Prognostic significance of epigenetic regulatory gene expression in patients with non-small-cell lung cancer Zegui Tu1,2, Xiancheng Chen4, Tian Tian1,2, Guo Chen5, Meijuan Huang1,2,3 1Department of Thoracic Oncology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China 2West China Medical School, Sichuan University, Chengdu 610041, P.R. China 3State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, P.R. China 4State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, P.R. China 5Global Infotech Software Limited Corporation, Chengdu 610041, Sichuan, P.R. China Correspondence to: Meijuan Huang; email: [email protected], https://orcid.org/0000-0002-3390-9697 Keywords: epigenetic regulatory genes, non-small-cell lung cancer, expression patterns, prognosis Received: May 28, 2020 Accepted: November 8, 2020 Published: February 26, 2021 Copyright: © 2021 Tu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT In this study, we used public databases to investigate the prognostic significance of epigenetic regulatory gene expression in patients with non small-cell lung cancer (NSCLC). Oncomine database analysis showed that the mRNA levels of seven epigenetic regulatory genes, UHRF1, EZH2, TTF2, SUV39H2, PCNA, WHSC1 and RAD54L, genes were significantly upregulated in NSCLC patients as compared to normal lung tissues.
    [Show full text]
  • Structure, Activity and Function of the Suv39h1 and Suv39h2 Protein Lysine Methyltransferases
    life Review Structure, Activity and Function of the Suv39h1 and Suv39h2 Protein Lysine Methyltransferases Sara Weirich 1, Mina S. Khella 1,2 and Albert Jeltsch 1,* 1 Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany; [email protected] (S.W.); [email protected] (M.S.K.) 2 Biochemistry Department, Faculty of Pharmacy, Ain Shams University, African Union Organization Street, Abbassia, Cairo 11566, Egypt * Correspondence: [email protected] Abstract: SUV39H1 and SUV39H2 were the first protein lysine methyltransferases that were identi- fied more than 20 years ago. Both enzymes introduce di- and trimethylation at histone H3 lysine 9 (H3K9) and have important roles in the maintenance of heterochromatin and gene repression. They consist of a catalytically active SET domain and a chromodomain, which binds H3K9me2/3 and has roles in enzyme targeting and regulation. The heterochromatic targeting of SUV39H enzymes is further enhanced by the interaction with HP1 proteins and repeat-associated RNA. SUV39H1 and SUV39H2 recognize an RKST motif with additional residues on both sides, mainly K4 in the case of SUV39H1 and G12 in the case of SUV39H2. Both SUV39H enzymes methylate different non-histone proteins including RAG2, DOT1L, SET8 and HupB in the case of SUV39H1 and LSD1 in the case of SUV39H2. Both enzymes are expressed in embryonic cells and have broad expression profiles in the adult body. SUV39H1 shows little tissue preference except thymus, while SUV39H2 is more highly expressed in the brain, testis and thymus. Both enzymes are connected to cancer, having oncogenic Citation: Weirich, S.; Khella, M.S.; or tumor-suppressive roles depending on the tumor type.
    [Show full text]