Imprinted Maternally-Expressed Micrornas Antagonize Paternally-Driven Gene Programs in Neurons
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Genomic Imprinting at the Porcine PLAGL1 Locus and the Orthologous Locus in the Human
G C A T T A C G G C A T genes Article Genomic Imprinting at the Porcine PLAGL1 Locus and the Orthologous Locus in the Human Jinsoo Ahn 1 , In-Sul Hwang 2 , Mi-Ryung Park 2, Seongsoo Hwang 2 and Kichoon Lee 1,* 1 Functional Genomics Laboratory, Department of Animal Sciences, The Ohio State University, Columbus, OH 43210, USA; [email protected] 2 Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Wanju, Jeonbuk 55365, Korea; [email protected] (I.-S.H.); [email protected] (M.-R.P.); [email protected] (S.H.) * Correspondence: [email protected]; Tel.: +1-614-688-7963 Abstract: Implementation of genomic imprinting in mammals often results in cis-acting silencing of a gene cluster and monoallelic expression, which are important for mammalian growth and function. Compared with widely documented imprinting status in humans and mice, current understanding of genomic imprinting in pigs is relatively limited. The objectives of this study were to identify DNA methylation status and allelic expression of alternative spliced isoforms at the porcine PLAGL1 locus and assess the conservation of the locus compared to the orthologous human locus. DNA methylome and transcriptome were constructed using porcine parthenogenetic or biparental control embryos. Using methylome, differentially methylated regions between those embryos were identified. Alternative splicing was identified by differential splicing analysis, and monoallelic expression was examined using single nucleotide polymorphism sites. Moreover, topological boundary regions were identified by analyzing CTCF binding sites and compared with the boundary of human orthologous locus. As a result, it was revealed that the monoallelic expression of the PLAGL1 Citation: Ahn, J.; Hwang, I.-S.; Park, M.-R.; Hwang, S.; Lee, K. -
Universidad Nacional Autónoma De México Plan De Estudios Combinados En Medicina Instituto Nacional De Medicina Genómica
UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO PLAN DE ESTUDIOS COMBINADOS EN MEDICINA INSTITUTO NACIONAL DE MEDICINA GENÓMICA ESTUDIO POST-MORTEM DE LAS ALTERACIONES EN LA EXPRESIÓN DE RNA EN EL CEREBRO DE PACIENTES SUICIDAS TESIS QUE PARA OPTAR POR EL GRADO DE DOCTORA EN MEDICINA PRESENTA: BRENDA CABRERA MENDOZA DIRECTOR DE TESIS: DR. JOSÉ HUMBERTO NICOLINI SÁNCHEZ INSTITUTO NACIONAL DE MEDICINA GENÓMICA COMITÉ TUTOR: DRA. MARTHA PATRICIA OSTROSKY-SHEJET INSTITUTO DE INVESTIGACIONES BIOMÉDICAS DR. DAVID COLIN GLAHN ESCUELA DE MEDICINA DE HARVARD Ciudad Universitaria, CD. MX., diciembre de 2020 TABLA DE CONTENIDOS Resumen ........................................................................................................................................................................ 1 Abstract .......................................................................................................................................................................... 2 Definición y epidemiología del suicidio ............................................................................................................ 3 Epidemiología global del suicidio ..................................................................................................................... 5 Epidemiología del suicidio en América ........................................................................................................... 8 Epidemiología del suicidio en México ............................................................................................................10 -
Zinc-Finger Protein 471 Suppresses Gastric Cancer Through
Oncogene (2018) 37:3601–3616 https://doi.org/10.1038/s41388-018-0220-5 ARTICLE Zinc-finger protein 471 suppresses gastric cancer through transcriptionally repressing downstream oncogenic PLS3 and TFAP2A 1 1 1 2 1 3 Lei Cao ● Shiyan Wang ● Yanquan Zhang ● Ka-Chun Wong ● Geicho Nakatsu ● Xiaohong Wang ● 1 3 1 Sunny Wong ● Jiafu Ji ● Jun Yu Received: 28 June 2017 / Revised: 23 December 2017 / Accepted: 23 February 2018 / Published online: 3 April 2018 © The Author(s) 2018. This article is published with open access Abstract Zinc-finger protein 471 (ZNF471) was preferentially methylated in gastric cancer using promoter methylation array. The role of ZNF471 in human cancer is unclear. Here we elucidated the functional significance, molecular mechanisms and clinical impact of ZNF471 in gastric cancer. ZNF471 mRNA was silenced in 15 out of 16 gastric cancer cell lines due to promoter hypermethylation. Significantly higher ZNF471 promoter methylation was also observed in primary gastric cancers compared to their adjacent normal tissues (P<0.001). ZNF471 promoter CpG-site hypermethylation correlated with poor 1234567890();,: survival of gastric cancer patients (n = 120, P = 0.001). Ectopic expression of ZNF471 in gastric cancer cell lines (AGS, BGC823, and MKN74) significantly suppressed cell proliferation, migration, and invasion, while it induced apoptosis in vitro and inhibited xenograft tumorigenesis in nude mice. Transcription factor AP-2 Alpha (TFAP2A) and plastin3 (PLS3) were two crucial downstream targets of ZNF471 demonstrated by bioinformatics modeling and ChIP-PCR assays. ZNF471 directly bound to the promoter of TFAP2A and PLS3 and transcriptionally inhibited their expression. TFAP2A and PLS3 showed oncogenic functions in gastric cancer cell lines. -
PLAGL1 (ZAC1/LOT1) Expression in Clear Cell Renal Cell Carcinoma: Correlations with Disease Progression and Unfavorable Prognosis
ANTICANCER RESEARCH 36: 617-624 (2016) PLAGL1 (ZAC1/LOT1) Expression in Clear Cell Renal Cell Carcinoma: Correlations with Disease Progression and Unfavorable Prognosis JANUSZ GODLEWSKI1, BARTLOMIEJ E. KRAZINSKI1, ANNA E. KOWALCZYK1, JOLANTA KIEWISZ1, JACEK KIEZUN1, PRZEMYSLAW KWIATKOWSKI1, AGNIESZKA SLIWINSKA-JEWSIEWICKA1, ZBIGNIEW MASLOWSKI2 and ZBIGNIEW KMIEC1,3 1Department of Human Histology and Embryology, Faculty of Medical Sciences, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland; 2Department of Oncological Surgery, Warmia and Mazury Oncological Center, Olsztyn, Poland; 3Department of Histology, Medical University of Gdansk, Gdansk, Poland Abstract. Background: Pleiomorphic adenoma gene-like 1 Clear cell renal cell carcinoma (ccRCC), the prevailing form (PLAGL1) protein was originally shown to induce cell-cycle of RCC, is characterized by the most aggressive behavior and arrest and promote apoptosis in several types of human poor prognosis among all types of kidney cancer (1-3). tumors and therefore it was considered a candidate tumor Although ccRCC tumors can be removed surgically, suppressor. The involvement of PLAGL1 gene in the etiology haematogeneous metastases frequently occur in the early and pathogenesis of clear cell renal cell carcinoma (ccRCC) stage of the disease and 35-65% of patients develop has not been evaluated. The purpose of the present study metastatic disease after nephrectomy (3). Over the past was to determine the expression level of PLAGL1 in ccRCC decade, the background of ccRCC pathogenesis has been and to investigate its potential utility as a prognostic factor. extensively screened for molecular biomarkers and relevant Materials and Methods: We applied quantitative real-time gene signatures, however, only few have significant polymerase chain reaction (QPCR), western blotting and prognostic value which can be used in clinical practice (3-5). -
Identification of Potential Key Genes and Pathway Linked with Sporadic Creutzfeldt-Jakob Disease Based on Integrated Bioinformatics Analyses
medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract Sporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened. -
The Melanocortin Receptors and Their Accessory Proteins. Ramachandrappa, S; Gorrigan, RJ; Clark, AJL; Chan, LF
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Queen Mary Research Online The melanocortin receptors and their accessory proteins. Ramachandrappa, S; Gorrigan, RJ; Clark, AJL; Chan, LF © 2013 Ramachandrappa, Gorrigan, Clark and Chan CC-BY For additional information about this publication click this link. http://qmro.qmul.ac.uk/xmlui/handle/123456789/18559 Information about this research object was correct at the time of download; we occasionally make corrections to records, please therefore check the published record when citing. For more information contact [email protected] REVIEW ARTICLE published: 08 February 2013 doi: 10.3389/fendo.2013.00009 The melanocortin receptors and their accessory proteins Shwetha Ramachandrappa, Rebecca J. Gorrigan, Adrian J. L. Clark and Li F. Chan* Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK Edited by: The five melanocortin receptors (MCRs) named MC1R–MC5R have diverse physiological Jae Young Seong, Korea University, roles encompassing pigmentation, steroidogenesis, energy homeostasis and feeding South Korea behavior as well as exocrine function. Since their identification almost 20 years ago much Reviewed by: has been learnt about these receptors. As well as interacting with their endogenous Akiyoshi Takahashi, Kitasato University, Japan ligands the melanocortin peptides, there is now a growing list of important peptides Robert Dores, University of that can modulate the way these receptors signal, acting as agonists, antagonists, and Minnesota, USA inverse agonists. The discovery of melanocortin 2 receptor accessory proteins as a novel *Correspondence: accessory factor to the MCRs provides further insight into the regulation of these important Li F.Chan, Centre for Endocrinology, G protein-coupled receptor. -
Altered Expression of the PLAGL1 (ZAC1/LOT1) Gene in Colorectal Cancer: Correlations to the Clinicopathological Parameters
INTERNATIONAL JOURNAL OF ONCOLOGY 47: 951-962, 2015 Altered expression of the PLAGL1 (ZAC1/LOT1) gene in colorectal cancer: Correlations to the clinicopathological parameters ANNA E. KowalcZYK1, Bartlomiej E. KRAZINSKI1, JANUSZ GODLEWSKI1, Jolanta KIEWISZ1, PRZEMYSlaw KwiatkowSKI1, AGNIESZKA SLIWINSKA-JEWSIEWICKA1, JACEK KIEZUN1, PIOTR M. WIERZBICKI2, GABRIEL BODEK3, MARIAN SULIK4 and ZBIGNIEW KMIEC1,2 1Department of Human Histology and Embryology, Faculty of Medical Sciences, University of Warmia and Mazury, 10-082 Olsztyn; 2Department of Histology, Medical University of Gdansk, 80-210 Gdansk; 3In Vitro and Cell Biotechnology Laboratory, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-243 Olsztyn; 4Department of Pathomorphology, Faculty of Medical Sciences, University of Warmia and Mazury, 10-561 Olsztyn, Poland Received April 23, 2015; Accepted June 2, 2015 DOI: 10.3892/ijo.2015.3067 Abstract. Pleomorphic adenoma gene-like 1 gene (PLAGL1) late significantly with patient overall survival; however, the encodes a zinc-finger nuclear transcription factor which hazard ratio for patients whose tumor tissues showed reduced promotes apoptosis and cell cycle arrest. Loss or downregu- PLAGL1 immunohistochemical staining was twice higher lation of its expression has been observed in various human than in patients with increased PLAGL1 immunoreactivity. In neoplasms. This study compared PLAGL1 expression in conclusion, these results suggest that dysregulation of PLAGL1 colorectal cancer (CRC) tissue and colon mucosa of healthy expression may be involved to some extent in the progression subjects at the mRNA and protein levels, and estimated its of CRC, but the so far collected patient survival data do not prognostic value. The PLAGL1 mRNA levels were also deter- confirm applicability of the PLAGL1 expression level as a mined in CRC cell lines. -
WO 2015/006437 Al 15 January 2015 (15.01.2015) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/006437 Al 15 January 2015 (15.01.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A01K 67/027 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/US2014/045934 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, July 2014 (09.07.2014) KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (25) Filing Language: English OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (26) Publication Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (30) Priority Data: ZW. 61/844,666 10 July 2013 (10.07.2013) US (84) Designated States (unless otherwise indicated, for every (72) Inventors; and kind of regional protection available): ARIPO (BW, GH, (71) Applicants : MAJZOUB, Joseph A. [US/US]; 1 Charles GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, St. South, Unit 9E, Boston, Massachusetts 021 16 (US). -
Genome-Wide DNA Methylation Dynamics During Epigenetic
Gómez‑Redondo et al. Clin Epigenet (2021) 13:27 https://doi.org/10.1186/s13148‑021‑01003‑x RESEARCH Open Access Genome‑wide DNA methylation dynamics during epigenetic reprogramming in the porcine germline Isabel Gómez‑Redondo1*† , Benjamín Planells1†, Sebastián Cánovas2,3, Elena Ivanova4, Gavin Kelsey4,5 and Alfonso Gutiérrez‑Adán1 Abstract Background: Prior work in mice has shown that some retrotransposed elements remain substantially methylated during DNA methylation reprogramming of germ cells. In the pig, however, information about this process is scarce. The present study was designed to examine the methylation profles of porcine germ cells during the time course of epigenetic reprogramming. Results: Sows were artifcially inseminated, and their fetuses were collected 28, 32, 36, 39, and 42 days later. At each time point, genital ridges were dissected from the mesonephros and germ cells were isolated through magnetic‑ activated cell sorting using an anti‑SSEA‑1 antibody, and recovered germ cells were subjected to whole‑genome bisulphite sequencing. Methylation levels were quantifed using SeqMonk software by performing an unbiased analysis, and persistently methylated regions (PMRs) in each sex were determined to extract those regions showing 50% or more methylation. Most genomic elements underwent a dramatic loss of methylation from day 28 to day 36, when the lowest levels were shown. By day 42, there was evidence for the initiation of genomic re‑methylation. We identifed a total of 1456 and 1122 PMRs in male and female germ cells, respectively, and large numbers of transpos‑ able elements (SINEs, LINEs, and LTRs) were found to be located within these PMRs. Twenty‑one percent of the introns located in these PMRs were found to be the frst introns of a gene, suggesting their regulatory role in the expression of these genes. -
Expression of KCNQ1OT1, CDKN1C, H19, and PLAGL1 and The
Robbins et al. Journal of Biomedical Science 2012, 19:95 http://www.jbiomedsci.com/content/19/1/95 RESEARCH Open Access Expression of KCNQ1OT1, CDKN1C, H19, and PLAGL1 and the methylation patterns at the KvDMR1 and H19/IGF2 imprinting control regions is conserved between human and bovine Katherine Marie Robbins, Zhiyuan Chen, Kevin Dale Wells and Rocío Melissa Rivera* Abstract Background: Beckwith-Wiedemann syndrome (BWS) is a loss-of-imprinting pediatric overgrowth syndrome. The primary features of BWS include macrosomia, macroglossia, and abdominal wall defects. Secondary features that are frequently observed in BWS patients are hypoglycemia, nevus flammeus, polyhydramnios, visceromegaly, hemihyperplasia, cardiac malformations, and difficulty breathing. BWS is speculated to occur primarily as the result of the misregulation of imprinted genes associated with two clusters on chromosome 11p15.5, namely the KvDMR1 and H19/IGF2. A similar overgrowth phenotype is observed in bovine and ovine as a result of embryo culture. In ruminants this syndrome is known as large offspring syndrome (LOS). The phenotypes associated with LOS are increased birth weight, visceromegaly, skeletal defects, hypoglycemia, polyhydramnios, and breathing difficulties. Even though phenotypic similarities exist between the two syndromes, whether the two syndromes are epigenetically similar is unknown. In this study we use control Bos taurus indicus X Bos taurus taurus F1 hybrid bovine concepti to characterize baseline imprinted gene expression and DNA methylation status of imprinted domains known to be misregulated in BWS. This work is intended to be the first step in a series of experiments aimed at determining if LOS will serve as an appropriate animal model to study BWS. -
Neonatal Diabetes Mellitus and Congenital
Topiol et al. International Journal of Pediatric Endocrinology 2012, 2012:21 http://www.ijpeonline.com/content/2012/1/21 CASE REPORT Open Access Neonatal diabetes mellitus and congenital diaphragmatic hernia: coincidence or concurrent etiology? Emmanuelle S Topiol1, Laurie A Minarich1, Charles A Williams2, Roberto T Zori2, David W Kays3 and Michael J Haller1* Abstract Neonatal diabetes mellitus (NDM) is a rare metabolic disorder, affecting approximately 1 in 500,000 live births. The management of NDM is challenging, as the benefits of controlling hyperglycemia must be balanced with the risks of iatrogenic hypoglycemia. NDM occurs in both permanent and transient forms, which have been genetically and phenotypically well characterized. Herein, we present the previously unreported combination of transient NDM (TNDM) and congenital diaphragmatic hernia (CDH). In addition to reviewing the management and genetics of NDM we discuss the potential for overlapping genetic or embryologic abnormalities to explain the concurrence of CDH and NDM. Keywords: Neonatal diabetes mellitus, Congenital diaphragmatic hernia, PLAGL1, Imprinting, Duplication Background Congenital diaphragmatic hernia (CDH) occurs in ap- Neonatal diabetes mellitus (NDM) is a rare disorder of proximately 1 in 2,500 children and results from a devel- glucose metabolism (affecting 1 in 500,000 live births) opmental defect in the diaphragm that allows abdominal and may be either transient or permanent [1]. Affected viscera to penetrate the chest [4]. Because the herniating neonates frequently present with hyperglycemia, intra- spleen, liver, and intestines may compress lung tissue uterine growth retardation, and variable degrees of dehy- during critical periods of lung organogenesis, CHD dration. Despite the relative severity of insulin results in varying degrees of irreversible pulmonary deficiency, ketoacidosis is uncommon. -
Gene Expression Profiling Identifies the Role of Zac1 in Cervical Cancer
www.nature.com/scientificreports OPEN Gene expression profling identifes the role of Zac1 in cervical cancer metastasis Hui‑Chen Su1,6, Sheng‑Cheng Wu2,6, Li‑Chen Yen3, Li‑Kang Chiao4, Jehng‑Kang Wang4, Yi‑Lin Chiu4,6*, Ching‑Liang Ho5 & Shih‑Ming Huang4,6* The zinc‑fnger protein which regulates apoptosis and cell cycle arrest 1 (Zac1), encoded by Plagl1 gene, is a seven‑zinc‑fnger containing transcription factor belonging to the imprinted genome and is expressed in diverse types of embryonic and adult human tissues. Zac1 is postulated to be a tumor suppressor by inducing cell cycle arrest and apoptosis through interacting and modulating transcriptional activity of p53 as it was named. Correspondingly, the reduction or loss of Zac1 expression is associated with the incidence and progression of several human tumors, including cervical cancer, breast cancer, ovarian cancer, pituitary tumors, and basal cell carcinoma, implying the rationality of utilizing Zac1 expression as novel a biomarker for the evaluation of cervical cancer prognosis. However, to date, it has not been elucidated whether Zac1 expression is related to the prognosis of patients in clinical cervical cancer tumor samples. To address the questions outlined above, we report here a comprehensive investigation of Zac1 expression in biopsies of clinical cervical carcinoma. By analyzing Zac1 expression in various gene expression profling of cervical cancer databases, we show the association between high Zac1 expression and poor prognosis of cervical cancer. Functional enrichment analysis showed that high Zac1 expression was associated with epithelial‑mesenchymal transition (EMT), which was further observed in clinical characteristics and metastatic carcinoma samples using immunohistochemical staining.