PRC1 Collaborates with SMCHD1 to Fold the X-Chromosome and Spread
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The HECT Domain Ubiquitin Ligase HUWE1 Targets Unassembled Soluble Proteins for Degradation
OPEN Citation: Cell Discovery (2016) 2, 16040; doi:10.1038/celldisc.2016.40 ARTICLE www.nature.com/celldisc The HECT domain ubiquitin ligase HUWE1 targets unassembled soluble proteins for degradation Yue Xu1, D Eric Anderson2, Yihong Ye1 1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; 2Advanced Mass Spectrometry Core Facility, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA In eukaryotes, many proteins function in multi-subunit complexes that require proper assembly. To maintain complex stoichiometry, cells use the endoplasmic reticulum-associated degradation system to degrade unassembled membrane subunits, but how unassembled soluble proteins are eliminated is undefined. Here we show that degradation of unassembled soluble proteins (referred to as unassembled soluble protein degradation, USPD) requires the ubiquitin selective chaperone p97, its co-factor nuclear protein localization protein 4 (Npl4), and the proteasome. At the ubiquitin ligase level, the previously identified protein quality control ligase UBR1 (ubiquitin protein ligase E3 component n-recognin 1) and the related enzymes only process a subset of unassembled soluble proteins. We identify the homologous to the E6-AP carboxyl terminus (homologous to the E6-AP carboxyl terminus) domain-containing protein HUWE1 as a ubiquitin ligase for substrates bearing unshielded, hydrophobic segments. We used a stable isotope labeling with amino acids-based proteomic approach to identify endogenous HUWE1 substrates. Interestingly, many HUWE1 substrates form multi-protein com- plexes that function in the nucleus although HUWE1 itself is cytoplasmically localized. Inhibition of nuclear entry enhances HUWE1-mediated ubiquitination and degradation, suggesting that USPD occurs primarily in the cytoplasm. -
Smchd1-Dependent and -Independent Pathways Determine Developmental Dynamics of Cpg Island Methylation on The
Edinburgh Research Explorer Smchd1-Dependent and -Independent Pathways Determine Developmental Dynamics of CpG Island Methylation on the Inactive X Chromosome Citation for published version: Gendrel, AV, Apedaile, A, Coker, H, Termanis, A, Zvetkova, I, Godwin, J, Montana, G, Taylor, S, Giannoulatou, E, Heard, E, Stancheva, I & Brockdorff, N 2012, 'Smchd1-Dependent and -Independent Pathways Determine Developmental Dynamics of CpG Island Methylation on the Inactive X Chromosome', Developmental Cell, vol. 23, no. 2, pp. 265–279. https://doi.org/10.1016/j.devcel.2012.06.011 Digital Object Identifier (DOI): 10.1016/j.devcel.2012.06.011 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: Developmental Cell General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 07. Oct. 2021 Developmental Cell Article Smchd1-Dependent and -Independent Pathways Determine Developmental Dynamics of CpG Island Methylation on the Inactive X Chromosome Anne-Valerie Gendrel,1,7,8 Anwyn Apedaile,3,8 Heather Coker,1 Ausma Termanis,4 Ilona Zvetkova,3,9 Jonathan Godwin,1 Y. -
Linked Mental Retardation Detected by Array CGH
JMG Online First, published on September 16, 2005 as 10.1136/jmg.2005.036178 J Med Genet: first published as 10.1136/jmg.2005.036178 on 16 September 2005. Downloaded from Chromosomal copy number changes in patients with non-syndromic X- linked mental retardation detected by array CGH D Lugtenberg1, A P M de Brouwer1, T Kleefstra1, A R Oudakker1, S G M Frints2, C T R M Schrander- Stumpel2, J P Fryns3, L R Jensen4, J Chelly5, C Moraine6, G Turner7, J A Veltman1, B C J Hamel1, B B A de Vries1, H van Bokhoven1, H G Yntema1 1Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; 2Department of Clinical Genetics, University Hospital Maastricht, Maastricht, The Netherlands; 3Center for Human Genetics, University of Leuven, Leuven, Belgium; 4Max Planck Institute for Molecular Genetics, Berlin, Germany; 5INSERM 129-ICGM, Faculté de Médecine Cochin, Paris, France; 6Service de Génétique et INSERM U316, Hôpital Bretonneau, Tours, France; 7 GOLD Program, Hunter Genetics, University of Newcastle, Callaghan, New South Wales 2308, Australia http://jmg.bmj.com/ Corresponding author: on October 2, 2021 by guest. Protected copyright. Helger G. Yntema, PhD Department of Human Genetics Radboud University Nijmegen Medical Centre P.O. Box 9101 6500 HB Nijmegen The Netherlands E-mail: [email protected] tel: +31-24-3613799 fax: +31-24-3616658 1 Copyright Article author (or their employer) 2005. Produced by BMJ Publishing Group Ltd under licence. J Med Genet: first published as 10.1136/jmg.2005.036178 on 16 September 2005. Downloaded from ABSTRACT Introduction: Several studies have shown that array based comparative genomic hybridization (array CGH) is a powerful tool for the detection of copy number changes in the genome of individuals with a congenital disorder. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Ageing-Associated Changes in DNA Methylation in X and Y Chromosomes
Kananen and Marttila Epigenetics & Chromatin (2021) 14:33 Epigenetics & Chromatin https://doi.org/10.1186/s13072-021-00407-6 RESEARCH Open Access Ageing-associated changes in DNA methylation in X and Y chromosomes Laura Kananen1,2,3,4* and Saara Marttila4,5* Abstract Background: Ageing displays clear sexual dimorphism, evident in both morbidity and mortality. Ageing is also asso- ciated with changes in DNA methylation, but very little focus has been on the sex chromosomes, potential biological contributors to the observed sexual dimorphism. Here, we sought to identify DNA methylation changes associated with ageing in the Y and X chromosomes, by utilizing datasets available in data repositories, comprising in total of 1240 males and 1191 females, aged 14–92 years. Results: In total, we identifed 46 age-associated CpG sites in the male Y, 1327 age-associated CpG sites in the male X, and 325 age-associated CpG sites in the female X. The X chromosomal age-associated CpGs showed signifcant overlap between females and males, with 122 CpGs identifed as age-associated in both sexes. Age-associated X chro- mosomal CpGs in both sexes were enriched in CpG islands and depleted from gene bodies and showed no strong trend towards hypermethylation nor hypomethylation. In contrast, the Y chromosomal age-associated CpGs were enriched in gene bodies, and showed a clear trend towards hypermethylation with age. Conclusions: Signifcant overlap in X chromosomal age-associated CpGs identifed in males and females and their shared features suggest that despite the uneven chromosomal dosage, diferences in ageing-associated DNA methylation changes in the X chromosome are unlikely to be a major contributor of sex dimorphism in ageing. -
A Midbody Component Homolog, Too Much Information/Prc1-Like, Is Required For
bioRxiv preprint doi: https://doi.org/10.1101/2021.06.10.447958; this version posted June 11, 2021. 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. A midbody component homolog, too much information/prc1-like, is required for microtubule reorganization during both cytokinesis and axis induction in the early zebrafish embryo Nair, S 1,2,*, 1Welch, E.L. 1,*, Moravec, C.E. 1, Trevena, R.L.1, Pelegri, F. 1 * shared first authorship 1. LaBoratory of Genetics, University of Wisconsin-Madison, Madison, WI, USA 2. Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, India Correspondence to: Francisco Pelegri at [email protected] 608-262-2920 Short title: zebrafish Prc-1L, cytokinesis and axis induction Key words: zebrafish, Prc-1, cytokinesis, midBody, microtuBule reorganization, axis induction bioRxiv preprint doi: https://doi.org/10.1101/2021.06.10.447958; this version posted June 11, 2021. 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. Abstract We show that the zeBrafish maternal-effect mutation too much information (tmi) corresponds to zebrafish prc1-like (prc1l), which encodes a member of the MAP65/Ase1/PRC1family of microtuBule-associated proteins. Embryos from tmi/prc1l homozygous mutant mothers display cytokinesis defects in meiotic and mitotic divisions in the early embryo, indicating that tmi/prc1l has a role in midBody formation during cell division at the egg-to-embryo transition. Unexpectedly, maternal tmi/prc1l function is also essential for the reorganization of vegetal pole microtuBules required for embryonic axis induction. -
Mouse Gm44504 Knockout Project (CRISPR/Cas9)
https://www.alphaknockout.com Mouse Gm44504 Knockout Project (CRISPR/Cas9) Objective: To create a Gm44504 knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Gm44504 gene (NCBI Reference Sequence: NM_001278271 ; Ensembl: ENSMUSG00000015290 ) is located on Mouse chromosome X. 7 exons are identified, with the ATG start codon in exon 4 and the TAG stop codon in exon 7 (Transcript: ENSMUST00000178691). Exon 6 will be selected as target site. Cas9 and gRNA will be co-injected into fertilized eggs for KO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Exon 6 starts from about 32.91% of the coding region. Exon 6 covers 44.37% of the coding region. The size of effective KO region: ~209 bp. The KO region does not have any other known gene. Page 1 of 9 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele 5' gRNA region gRNA region 3' 1 6 7 Legends Exon of mouse Gm44504 Knockout region Page 2 of 9 https://www.alphaknockout.com Overview of the Dot Plot (up) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 209 bp section of Exon 6 is aligned with itself to determine if there are tandem repeats. No significant tandem repeat is found in the dot plot matrix. So this region is suitable for PCR screening or sequencing analysis. Overview of the Dot Plot (down) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 209 bp section of Exon 6 is aligned with itself to determine if there are tandem repeats. -
VU Research Portal
VU Research Portal Genetic architecture and behavioral analysis of attention and impulsivity Loos, M. 2012 document version Publisher's PDF, also known as Version of record Link to publication in VU Research Portal citation for published version (APA) Loos, M. (2012). Genetic architecture and behavioral analysis of attention and impulsivity. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. E-mail address: [email protected] Download date: 28. Sep. 2021 Genetic architecture and behavioral analysis of attention and impulsivity Maarten Loos 1 About the thesis The work described in this thesis was performed at the Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands. This work was in part funded by the Dutch Neuro-Bsik Mouse Phenomics consortium. The Neuro-Bsik Mouse Phenomics consortium was supported by grant BSIK 03053 from SenterNovem (The Netherlands). -
Myopia in African Americans Is Significantly Linked to Chromosome 7P15.2-14.2
Genetics Myopia in African Americans Is Significantly Linked to Chromosome 7p15.2-14.2 Claire L. Simpson,1,2,* Anthony M. Musolf,2,* Roberto Y. Cordero,1 Jennifer B. Cordero,1 Laura Portas,2 Federico Murgia,2 Deyana D. Lewis,2 Candace D. Middlebrooks,2 Elise B. Ciner,3 Joan E. Bailey-Wilson,1,† and Dwight Stambolian4,† 1Department of Genetics, Genomics and Informatics and Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, United States 2Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland, United States 3The Pennsylvania College of Optometry at Salus University, Elkins Park, Pennsylvania, United States 4Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States Correspondence: Joan E. PURPOSE. The purpose of this study was to perform genetic linkage analysis and associ- Bailey-Wilson, NIH/NHGRI, 333 ation analysis on exome genotyping from highly aggregated African American families Cassell Drive, Suite 1200, Baltimore, with nonpathogenic myopia. African Americans are a particularly understudied popula- MD 21131, USA; tion with respect to myopia. [email protected]. METHODS. One hundred six African American families from the Philadelphia area with a CLS and AMM contributed equally to family history of myopia were genotyped using an Illumina ExomePlus array and merged this work and should be considered co-first authors. with previous microsatellite data. Myopia was initially measured in mean spherical equiv- JEB-W and DS contributed equally alent (MSE) and converted to a binary phenotype where individuals were identified as to this work and should be affected, unaffected, or unknown. -
Transcriptional Regulation of the P16 Tumor Suppressor Gene
ANTICANCER RESEARCH 35: 4397-4402 (2015) Review Transcriptional Regulation of the p16 Tumor Suppressor Gene YOJIRO KOTAKE, MADOKA NAEMURA, CHIHIRO MURASAKI, YASUTOSHI INOUE and HARUNA OKAMOTO Department of Biological and Environmental Chemistry, Faculty of Humanity-Oriented Science and Engineering, Kinki University, Fukuoka, Japan Abstract. The p16 tumor suppressor gene encodes a specifically bind to and inhibit the activity of cyclin-CDK specific inhibitor of cyclin-dependent kinase (CDK) 4 and 6 complexes, thus preventing G1-to-S progression (4, 5). and is found altered in a wide range of human cancers. p16 Among these CKIs, p16 plays a pivotal role in the regulation plays a pivotal role in tumor suppressor networks through of cellular senescence through inhibition of CDK4/6 activity inducing cellular senescence that acts as a barrier to (6, 7). Cellular senescence acts as a barrier to oncogenic cellular transformation by oncogenic signals. p16 protein is transformation induced by oncogenic signals, such as relatively stable and its expression is primary regulated by activating RAS mutations, and is achieved by accumulation transcriptional control. Polycomb group (PcG) proteins of p16 (Figure 1) (8-10). The loss of p16 function is, associate with the p16 locus in a long non-coding RNA, therefore, thought to lead to carcinogenesis. Indeed, many ANRIL-dependent manner, leading to repression of p16 studies have shown that the p16 gene is frequently mutated transcription. YB1, a transcription factor, also represses the or silenced in various human cancers (11-14). p16 transcription through direct association with its Although many studies have led to a deeper understanding promoter region. -
Gfh 2016 Tagungsband Final.Pdf
27. Jahrestagung der Deutschen Gesellschaft für Humangenetik 27. Jahrestagung der Deutschen Gesellschaft für Humangenetik gemeinsam mit der Österreichischen Gesellschaft für Humangenetik und der Schweizerischen Gesellschaft für Medizinische Genetik 16.–18. 3. 2016, Lübeck Tagungsort Prof. Dr. med. Jörg Epplen, Bochum (Tagungspräsident 2017) Prof. Dr. med. Michael Speicher, Graz (Tagungspräsident 2015) Hotel Hanseatischer Hof Prof. Dr. med. Klaus Zerres, Aachen Wisbystraße 7–9 Prof. Dr. rer. nat. Wolfgang Berger, Zürich (Delegierter der SGMG) 23558 Lübeck Univ.-Prof. DDr. med. univ. Johannes Zschocke, Telefon: (0451) 3 00 20-0 (Innsbruck Delegierter der ÖGH) http://www.hanseatischer- hof.de/ [email protected] Fachgesellschaften Die Jahrestagung fi ndet im Hotel Hanseatischer Hof statt, das sich Deutsche Gesellschaft für Humangenetik (GfH) in in fussläufi ger Entfernung vom Lübecker Hauptbahnhof befi ndet. Vorsitzender: Prof. Dr. med. Klaus Zerres, Aachen Stellvertretende Vorsitzende: Prof. Dr. med. Gabriele Gillessen- Tagungspräsidentin Kaesbach, Lübeck Stellvertretende Vorsitzende: Prof. Dr. biol. hum. Hildegard Prof. Dr. med. Gabriele Gillessen- Kaesbach Kehrer- Sawatzki, Ulm Institut für Humangenetik Schatzmeister: Dr. rer. nat. Wolfram Kress, Würzburg Universität zu Lübeck/UKSH Schrift führerin: Dr. rer. nat. Simone Heidemann, Kiel Ratzeburger Allee 160, Haus 72 23538 Lübeck Österreichische Gesellschaft für Humangenetik (ÖGH) Telefon: 0049-451-500-2620 Univ. Prof. Dr. med. univ. Michael Speicher, Graz (Vorsitzender) Fax: 0049-451-500-4187 Univ. Doz. Dr. med. univ. Hans-Christoph Duba, Linz (Stellvertre- tende Vorsitzende) Tagungsorganisation Univ.-Prof. DDr. med. univ. Johannes Zschocke, Innsbruck (Stellvertretende Vorsitzende) Dr. Christine Scholz (Leitung) Dr. Gerald Webersinke, Linz (Schrift führer) Brigitte Fiedler (Teilnehmerregistrierung) Ass.-Prof. Priv. Doz. Dr. med. univ. Franco Laccone, Wien (Stellver- Deutsche Gesellschaft für Humangenetik e. -
Mouse Plxnb3 Knockout Project (CRISPR/Cas9)
https://www.alphaknockout.com Mouse Plxnb3 Knockout Project (CRISPR/Cas9) Objective: To create a Plxnb3 knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Plxnb3 gene (NCBI Reference Sequence: NM_019587 ; Ensembl: ENSMUSG00000031385 ) is located on Mouse chromosome X. 35 exons are identified, with the ATG start codon in exon 2 and the TGA stop codon in exon 35 (Transcript: ENSMUST00000002079). Exon 2~15 will be selected as target site. Cas9 and gRNA will be co-injected into fertilized eggs for KO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Mice homozygous for a knock-out allele exhibit normal retinal stratification. Exon 2 starts from the coding region. Exon 2~15 covers 48.05% of the coding region. The size of effective KO region: ~6850 bp. The KO region does not have any other known gene. Page 1 of 9 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele 5' gRNA region gRNA region 3' 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 35 Legends Exon of mouse Plxnb3 Knockout region Page 2 of 9 https://www.alphaknockout.com Overview of the Dot Plot (up) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 1372 bp section upstream of Exon 2 is aligned with itself to determine if there are tandem repeats. No significant tandem repeat is found in the dot plot matrix. So this region is suitable for PCR screening or sequencing analysis. Overview of the Dot Plot (down) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 632 bp section downstream of Exon 15 is aligned with itself to determine if there are tandem repeats.