The Genetics of Human Infertility by Functional Interrogation of Snps in Mice
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Meiotic Cohesin and Variants Associated with Human Reproductive Aging and Disease
fcell-09-710033 July 27, 2021 Time: 16:27 # 1 REVIEW published: 02 August 2021 doi: 10.3389/fcell.2021.710033 Meiotic Cohesin and Variants Associated With Human Reproductive Aging and Disease Rachel Beverley1, Meredith L. Snook1 and Miguel Angel Brieño-Enríquez2* 1 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, United States, 2 Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, United States Successful human reproduction relies on the well-orchestrated development of competent gametes through the process of meiosis. The loading of cohesin, a multi- protein complex, is a key event in the initiation of mammalian meiosis. Establishment of sister chromatid cohesion via cohesin rings is essential for ensuring homologous recombination-mediated DNA repair and future proper chromosome segregation. Cohesin proteins loaded during female fetal life are not replenished over time, and therefore are a potential etiology of age-related aneuploidy in oocytes resulting in Edited by: decreased fecundity and increased infertility and miscarriage rates with advancing Karen Schindler, Rutgers, The State University maternal age. Herein, we provide a brief overview of meiotic cohesin and summarize of New Jersey, United States the human genetic studies which have identified genetic variants of cohesin proteins and Reviewed by: the associated reproductive phenotypes -
Atrec8 and Atscc3 Are Essential to the Monopolar Orientation of the Kinetochores During Meiosis
Research Article 4621 AtREC8 and AtSCC3 are essential to the monopolar orientation of the kinetochores during meiosis Liudmila Chelysheva, Stéphanie Diallo*, Daniel Vezon, Ghislaine Gendrot, Nathalie Vrielynck, Katia Belcram, Nathalie Rocques, Angustias Márquez-Lema‡, Anuj M. Bhatt§, Christine Horlow, Raphaël Mercier, Christine Mézard and Mathilde Grelon¶ Institut Jean-Pierre Bourgin, Station de Génétique et d’Amélioration des Plantes, INRA de Versailles, Route de Saint-Cyr, 78026 Versailles CEDEX, France *Present address: Laboratoire de Microbiologie du Froid UPRES 2123, 55 Rue Saint-Germain, 27000 Evreux, France ‡Present address: Instituto de Agricultura Sostenible (CSIC), Apartado 4084, E-14080, Córdoba, Spain §Present address: Department of Plant Sciences, University of Oxford, South Parks Road, Oxford, OX1 3RB, UK ¶Author for correspondence (e-mail: [email protected]) Accepted 13 July 2005 Journal of Cell Science 118, 4621-4632 Published by The Company of Biologists 2005 doi:10.1242/jcs.02583 Summary The success of the first meiotic division relies (among other in meiotic nuclei as early as interphase, and bound to the factors) on the formation of bivalents between homologous chromosome axis from early leptotene through to anaphase chromosomes, the monopolar orientation of the sister I. We show here that both AtREC8 and AtSCC3 are kinetochores at metaphase I and the maintenance of necessary not only to maintain centromere cohesion at centromeric cohesion until the onset of anaphase II. The anaphase I, but also for the monopolar orientation of the meiotic cohesin subunit, Rec8 has been reported to be one kinetochores during the first meiotic division. We also of the key players in these processes, but its precise role in found that AtREC8 is involved in chromosome axis kinetochore orientation is still under debate. -
Evolution, Expression and Meiotic Behavior of Genes Involved in Chromosome Segregation of Monotremes
G C A T T A C G G C A T genes Article Evolution, Expression and Meiotic Behavior of Genes Involved in Chromosome Segregation of Monotremes Filip Pajpach , Linda Shearwin-Whyatt and Frank Grützner * School of Biological Sciences, The University of Adelaide, Adelaide, SA 5005, Australia; fi[email protected] (F.P.); [email protected] (L.S.-W.) * Correspondence: [email protected] Abstract: Chromosome segregation at mitosis and meiosis is a highly dynamic and tightly regulated process that involves a large number of components. Due to the fundamental nature of chromosome segregation, many genes involved in this process are evolutionarily highly conserved, but duplica- tions and functional diversification has occurred in various lineages. In order to better understand the evolution of genes involved in chromosome segregation in mammals, we analyzed some of the key components in the basal mammalian lineage of egg-laying mammals. The chromosome passenger complex is a multiprotein complex central to chromosome segregation during both mitosis and meio- sis. It consists of survivin, borealin, inner centromere protein, and Aurora kinase B or C. We confirm the absence of Aurora kinase C in marsupials and show its absence in both platypus and echidna, which supports the current model of the evolution of Aurora kinases. High expression of AURKBC, an ancestor of AURKB and AURKC present in monotremes, suggests that this gene is performing all necessary meiotic functions in monotremes. Other genes of the chromosome passenger complex complex are present and conserved in monotremes, suggesting that their function has been preserved Citation: Pajpach, F.; in mammals. -
The N-Cadherin Interactome in Primary Cardiomyocytes As Defined Using Quantitative Proximity Proteomics Yang Li1,*, Chelsea D
© 2019. Published by The Company of Biologists Ltd | Journal of Cell Science (2019) 132, jcs221606. doi:10.1242/jcs.221606 TOOLS AND RESOURCES The N-cadherin interactome in primary cardiomyocytes as defined using quantitative proximity proteomics Yang Li1,*, Chelsea D. Merkel1,*, Xuemei Zeng2, Jonathon A. Heier1, Pamela S. Cantrell2, Mai Sun2, Donna B. Stolz1, Simon C. Watkins1, Nathan A. Yates1,2,3 and Adam V. Kwiatkowski1,‡ ABSTRACT requires multiple adhesion, cytoskeletal and signaling proteins, The junctional complexes that couple cardiomyocytes must transmit and mutations in these proteins can cause cardiomyopathies (Ehler, the mechanical forces of contraction while maintaining adhesive 2018). However, the molecular composition of ICD junctional homeostasis. The adherens junction (AJ) connects the actomyosin complexes remains poorly defined. – networks of neighboring cardiomyocytes and is required for proper The core of the AJ is the cadherin catenin complex (Halbleib and heart function. Yet little is known about the molecular composition of the Nelson, 2006; Ratheesh and Yap, 2012). Classical cadherins are cardiomyocyte AJ or how it is organized to function under mechanical single-pass transmembrane proteins with an extracellular domain that load. Here, we define the architecture, dynamics and proteome of mediates calcium-dependent homotypic interactions. The adhesive the cardiomyocyte AJ. Mouse neonatal cardiomyocytes assemble properties of classical cadherins are driven by the recruitment of stable AJs along intercellular contacts with organizational and cytosolic catenin proteins to the cadherin tail, with p120-catenin β structural hallmarks similar to mature contacts. We combine (CTNND1) binding to the juxta-membrane domain and -catenin β quantitative mass spectrometry with proximity labeling to identify the (CTNNB1) binding to the distal part of the tail. -
Derivation of Hypermethylated Pluripotent Embryonic Stem Cells with High Potency
Cell Research (2018) 28:22-34. ORIGINAL ARTICLE www.nature.com/cr Derivation of hypermethylated pluripotent embryonic stem cells with high potency Siqin Bao1, 2, Walfred WC Tang3, Baojiang Wu2, Shinseog Kim3, 8, Jingyun Li4, Lin Li4, Toshihiro Kobayashi3, Caroline Lee3, Yanglin Chen2, Mengyi Wei2, Shudong Li5, Sabine Dietmann6, Fuchou Tang4, Xihe Li1, 2, 7, M Azim Surani3 1The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China; 2Research Center for Animal Genetic Resources of Mongolia Plateau, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China; 3Wellcome Trust Cancer Research UK Gurdon Institute, Tennis Court Road, University of Cam- bridge, Cambridge CB2 1QN, UK; 4BIOPIC, School of Life Sciences, Peking University, Beijing 100871, China; 5Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Ox- ford OX3 7DQ, UK; 6Wellcome Trust-Medical Research Council Stem Cell Institute, Tennis Court Road, University of Cambridge, Cambridge CB2 3EG, UK; 7Inner Mongolia Saikexing Institute of Breeding and Reproductive Biotechnology in Domestic Animal, Hohhot 011517, China Naive hypomethylated embryonic pluripotent stem cells (ESCs) are developmentally closest to the preimplanta- tion epiblast of blastocysts, with the potential to contribute to all embryonic tissues and the germline, excepting the extra-embryonic tissues in chimeric embryos. By contrast, epiblast stem cells (EpiSCs) resembling postimplantation epiblast are relatively more methylated and show a limited potential for chimerism. Here, for the first time, we re- veal advanced pluripotent stem cells (ASCs), which are developmentally beyond the pluripotent cells in the inner cell mass but with higher potency than EpiSCs. -
Identification of Novel Y Chromosome Encoded Transcripts by Testis Transcriptome Analysis of Mice with Deletions of the Y Chromo
Open Access Research2005TouréetVolume al. 6, Issue 12, Article R102 Identification of novel Y chromosome encoded transcripts by testis comment transcriptome analysis of mice with deletions of the Y chromosome long arm Aminata Touré¤*, Emily J Clemente¤†, Peter JI Ellis†, Shantha K Mahadevaiah*, Obah A Ojarikre*, Penny AF Ball‡, Louise Reynard*, Kate L Loveland‡, Paul S Burgoyne* and Nabeel A Affara† reviews Addresses: *Division of Developmental Genetics, MRC National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK. †University of Cambridge, Department of Pathology, Tennis Court Road, Cambridge, CB2 1QP, UK. ‡Monash Institute of Medical Research, Monash University, and The Australian Research Council Centre of Excellence in Biotechnology and Development, Melbourne, Victoria 3168 Australia. ¤ These authors contributed equally to this work. Correspondence: Paul S Burgoyne. E-mail: [email protected] reports Published: 2 December 2005 Received: 17 June 2005 Revised: 19 September 2005 Genome Biology 2005, 6:R102 (doi:10.1186/gb-2005-6-12-r102) Accepted: 27 October 2005 The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2005/6/12/R102 deposited research © 2005 Touré et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Y<p>Microarraymosome chromosome long arm -analysis encoded (MSYq) of mouse identifiedthe changes testis novel transcripts in the Y chromosome-encoded testis transcriptome resulting transcripts.</p> from deletions of the male-specific region on the mouse chro- Abstract Background: The male-specific region of the mouse Y chromosome long arm (MSYq) is research refereed comprised largely of repeated DNA, including multiple copies of the spermatid-expressed Ssty gene family. -
'Histology and Immunophenotype of Invasive Lobular Breast Cancer
Varga, Z; Mallon, E (2009). Histology and Immunophenotype of Invasive Lobular Breast Cancer. Daily Practice and Pitfalls. Breast Disease, 30:15-19. Postprint available at: http://www.zora.uzh.ch University of Zurich Posted at the Zurich Open Repository and Archive, University of Zurich. Zurich Open Repository and Archive http://www.zora.uzh.ch Originally published at: Breast Disease 2009, 30:15-19. Winterthurerstr. 190 CH-8057 Zurich http://www.zora.uzh.ch Year: 2009 Histology and Immunophenotype of Invasive Lobular Breast Cancer. Daily Practice and Pitfalls Varga, Z; Mallon, E Varga, Z; Mallon, E (2009). Histology and Immunophenotype of Invasive Lobular Breast Cancer. Daily Practice and Pitfalls. Breast Disease, 30:15-19. Postprint available at: http://www.zora.uzh.ch Posted at the Zurich Open Repository and Archive, University of Zurich. http://www.zora.uzh.ch Originally published at: Breast Disease 2009, 30:15-19. Histology and Immunophenotype of Invasive Lobular Breast Cancer. Daily Practice and Pitfalls Abstract Invasive lobular carcinomas (ILC) represent the most common subtype of invasive breast cancer and account for about 5-15% of all breast cancer cases. Invasive lobular carcinoma is often accompanied by in situ lesions, by lobular neoplasia (LN). Invasive lobular carcinomas display diverse histologic patterns varying from classical through solid to pleomorphic subtypes. When analyzing histological subtypes, the classical variant is reported to have a more favorable outcome. The majority of invasive lobular carcinomas are hormone receptor positive, overexpression and/or amplification of the Her2 gene is lower than in carcinomas of invasive ductal type. Loss of heterozygosity of the 16q chromosomal regions and the consequent lack of E-Cadherin expression are common findings in invasive lobular carcinomas. -
CDH1 Gene Cadherin 1
CDH1 gene cadherin 1 Normal Function The CDH1 gene provides instructions for making a protein called epithelial cadherin or E-cadherin. This protein is found within the membrane that surrounds epithelial cells, which are the cells that line the surfaces and cavities of the body, such as the inside of the eyelids and mouth. E-cadherin belongs to a family of proteins called cadherins whose function is to help neighboring cells stick to one another (cell adhesion) to form organized tissues. Another protein called p120-catenin, produced from the CTNND1 gene, helps keep E-cadherin in its proper place in the cell membrane, preventing it from being taken into the cell through a process called endocytosis and broken down prematurely. E-cadherin is one of the best-understood cadherin proteins. In addition to its role in cell adhesion, E-cadherin is involved in transmitting chemical signals within cells, controlling cell maturation and movement, and regulating the activity of certain genes. Interactions between the E-cadherin and p120-catenin proteins, in particular, are thought to be important for normal development of the head and face (craniofacial development), including the eyelids and teeth. E-cadherin also acts as a tumor suppressor protein, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way. Health Conditions Related to Genetic Changes Breast cancer Inherited mutations in the CDH1 gene increase a woman's risk of developing a form of breast cancer that begins in the milk-producing glands (lobular breast cancer). In many cases, this increased risk occurs as part of an inherited cancer disorder called hereditary diffuse gastric cancer (HDGC) (described below). -
Studies of Epigenetic Deregulation in Parathyroid Tumors and Small Intestinal Neuroendocrine Tumors
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1377 Studies of epigenetic deregulation in parathyroid tumors and small intestinal neuroendocrine tumors ELHAM BARAZEGHI ACTA UNIVERSITATIS UPSALIENSIS ISSN 1651-6206 ISBN 978-91-513-0097-9 UPPSALA urn:nbn:se:uu:diva-330810 2017 Dissertation presented at Uppsala University to be publicly examined in Fåhraeussalen, Rudbecklaboratoriet Hus 5, Dag Hammarskjölds väg 20, Uppsala, Friday, 24 November 2017 at 13:15 for the degree of Doctor of Philosophy (Faculty of Medicine). The examination will be conducted in English. Faculty examiner: Associate Professor Christofer Juhlin (Department of Oncology-Pathology, Karolinska Institute). Abstract Barazeghi, E. 2017. Studies of epigenetic deregulation in parathyroid tumors and small intestinal neuroendocrine tumors. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1377. 53 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-513-0097-9. Deregulation of the epigenome is associated with the initiation and progression of various types of human cancers. Here we investigated the level of 5-hydroxymethylcytosine (5hmC), expression and function of TET1 and TET2, and DNA methylation in parathyroid tumors and small intestinal neuroendocrine tumors (SI-NETs). In Paper I, an undetectable/very low level of 5hmC in parathyroid carcinomas (PCs) compared to parathyroid adenomas with positive staining, suggested that 5hmC may represent a novel biomarker for parathyroid malignancy. Immunohistochemistry revealed that increased tumor weight in adenomas was associated with a more aberrant staining pattern of 5hmC and TET1. A growth regulatory role of TET1 was demonstrated in parathyroid tumor cells. Paper II revealed that the expression of TET2 was also deregulated in PCs, and promoter hypermethylation was detected in PCs when compared to normal parathyroid tissues. -
Low Tolerance for Transcriptional Variation at Cohesin Genes Is Accompanied by Functional Links to Disease-Relevant Pathways
bioRxiv preprint doi: https://doi.org/10.1101/2020.04.11.037358; this version posted April 13, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Title Low tolerance for transcriptional variation at cohesin genes is accompanied by functional links to disease-relevant pathways Authors William Schierdingǂ1, Julia Horsfieldǂ2,3, Justin O’Sullivan1,3,4 ǂTo whom correspondence should be addressed. 1 Liggins Institute, The University of Auckland, Auckland, New Zealand 2 Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand 3 The Maurice Wilkins Centre for Biodiscovery, The University of Auckland, Auckland, New Zealand 4 MRC Lifecourse Epidemiology Unit, University of Southampton Acknowledgements This work was supported by a Royal Society of New Zealand Marsden Grant to JH and JOS (16-UOO- 072), and WS was supported by the same grant. Contributions WS planned the study, performed analyses, and drafted the manuscript. JH and JOS revised the manuscript. Competing interests None declared. bioRxiv preprint doi: https://doi.org/10.1101/2020.04.11.037358; this version posted April 13, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract Variants in DNA regulatory elements can alter the regulation of distant genes through spatial- regulatory connections. -
Supplementary Materials
Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine -
Somatic Mutational Landscapes of Adherens Junctions and Their
1 Somatic mutational landscapes of adherens junctions and their 2 functional consequences in cutaneous melanoma development 3 4 Praveen Kumar Korla,1 Chih-Chieh Chen,2 Daniel Esguerra Gracilla,1 Ming-Tsung Lai,3 Chih- 5 Mei Chen,4 Huan Yuan Chen,5 Tritium Hwang,1 Shih-Yin Chen,4,6,* Jim Jinn-Chyuan Sheu1,4, 6-9,* 6 1Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 80242, Taiwan; 7 2Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, 8 Taiwan; 3Department of Pathology, Taichung Hospital, Ministry of Health and Welfare, Taichung 9 40343, Taiwan; 4Genetics Center, China Medical University Hospital, Taichung 40447, Taiwan; 10 5Institute of Biomedical Sciences, Academia Sinica, Taipei 11574, Taiwan; 6School of Chinese 11 Medicine, China Medical University, Taichung 40402, Taiwan; 7Department of Health and 12 Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan; 8Department of 13 Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; 9Institute of 14 Biopharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung 80242, Taiwan 15 16 PKK, CCC and DEG contributed equally to this study. 17 *Correspondence to: Dr. Shih-Yin Chen ([email protected]) at Genetics Center, China 18 Medical University Hospital, Taichung, 40447, TAIWAN; or Dr. Jim Jinn-Chyuan Sheu 19 ([email protected]) at Institute of Biomedical Sciences, National Sun Yat-sen 20 University, Kaohsiung City 80424, TAIWAN. 21 22 Running title: mutational landscape of cadherins in melanoma 1 23 Abstract 24 Cell-cell interaction in skin homeostasis is tightly controlled by adherens junctions (AJs). 25 Alterations in such regulation lead to melanoma development.