Development & Differentiation
- MicroRNA‐455 regulates brown adipogenesis via a novel HIF1an‐AMPK‐PGC1α signaling network
- Hongbin Zhang*,1,2,
- Meiping Guan1,3,
- Kristy L Townsend1,
- Tian Lian Huang1,
- Ding An1,
- Xu Yan1,
- Ruidan Xue1,
- Tim J Schulz1,4,
- Jonathon Winnay1,
- Marcelo Mori1,5,
- Michael F Hirshman1,
- Karsten Kristiansen6,
- John S Tsang7,
- Andrew P White8,
- Aaron M Cypess1,
- Laurie J Goodyear1 and
- Yu‐Hua Tseng*,1,9
- 1Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
- 2Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
- 3Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
- 4Adipocyte Development Research Group, German Institute of Human Nutrition, Potsdam, Germany
- 5Department of Biophysics, Federal University of Sao Paulo, Sao Paulo, Brazil
- 6Department of Biology, University of Copenhagen, Copenhagen, Denmark
- 7Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases (NIAID) and Trans‐NIH Center for Human Immunology, National Institutes of Health, Bethesda, MD, USA
- 8Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- 9Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA
- ↵*
Corresponding author. Tel: +1 45 3533 0484; E‐mail: hongbin{at}sund.ku.dk
Corresponding author. Tel: +1 617 309 1967; Fax: +1 617 309 2650; E‐mail: yu-hua.tseng{at}joslin.harvard.edu
miR‐455 promotes brown adipocyte differentiation and thermogenesis by targeting the key adipogenic inhibitors Necdin and Runx1t1 and by inducing a HIF1an‐AMPK‐PGC1α signaling cascade stimulating mitochondria biogenesis.
Synopsis
miR‐455 promotes brown adipocyte differentiation and thermogenesis by targeting the key adipogenic inhibitors Necdin and Runx1t1 and by inducing a HIF1an‐AMPK‐PGC1α signaling cascade stimulating mitochondria biogenesis.
miR‐455 is expressed in brown adipose tissue and induced by cold.
Fat‐specific miR‐455 transgenic mice show browning of subcutaneous white fat upon cold exposure.
miR‐455 induces brown/beige adipogenesis by targeting key brown adipogenic inhibitors such as Runx1t1 and Necdin.
miR‐455 activates a HIF1an‐AMPK‐PGC1α signaling cascade that promotes thermogenesis.
EMBO Reports (2015) 16: 1378–1393
- Received June 11, 2015.
- Revision received July 19, 2015.
- Accepted July 24, 2015.
- © 2015 The Authors
- Venus trap in the mouse embryo reveals distinct molecular dynamics underlying specification of first embryonic lineages
- Jens‐Erik Dietrich15†,
- Laura Panavaite1,†,
- Stefan Gunther2,
- Sebastian Wennekamp1,
- Anna C Groner36,
- Anton Pigge4,
- Stefanie Salvenmoser1,
- Didier Trono3,
- Lars Hufnagel2 and
- Takashi Hiiragi*,1
- 1Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
- 2Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
- 3School of Life Sciences Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
- 4Max Planck Institute for Molecular Biomedicine, Muenster, Germany
- 5Department of Gynecologic Endocrinology and Fertility Disorders, Heidelberg University Women's Hospital, Heidelberg, Germany
- 6 Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana‐Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- ↵*Corresponding author. Tel: +49 6221 3878844; E‐mail: hiiragi{at}embl.de
↵† These authors contributed equally to this work
Systematic analyses of a comprehensive map of mouse pre‐implantation development reveal that the timing and mechanism of lineage specification may be different between the trophectoderm and the inner cell mass.
Synopsis
Systematic analyses of a comprehensive map of mouse pre‐implantation development reveal that the timing and mechanism of lineage specification may be different between the trophectoderm and the inner cell mass.
Venus‐trap screen in the mouse blastocyst generates fluorescent lineage reporter mice.
A comprehensive lineage map of mouse pre‐implantation development integrates lineage track, cell position and gene expression dynamics.
Systematic analyses of the map represent a framework toward systems‐level understanding of embryogenesis marked by high dynamicity and variability.
EMBO Reports (2015) 16: 1005–1021
- Received January 27, 2015.
- Revision received June 2, 2015.
- Accepted June 2, 2015.
- © 2015 The Authors
- Brahma is required for cell cycle arrest and late muscle gene expression during skeletal myogenesis
- Sonia Albini1,†,
- Paula Coutinho Toto1,†,
- Alessandra Dall'Agnese1,
- Barbora Malecova1,
- Carlo Cenciarelli2,
- Armando Felsani3,
- Maurizia Caruso3,
- Scott J Bultman4 and
- Pier Lorenzo Puri*,1,5
- 1Sanford‐Burnham Institute for Medical Research, La Jolla, CA, USA
- 2CNR‐Istituto di Farmacologia Traslazionale, Rome, Italy
- 3CNR‐Istituto di Biologia Cellulare e Neurobiologia Fondazione Santa Lucia, Rome, Italy
- 4Department of Genetics, Lineberger Comprehensive Cancer Center University of North Carolina, Chapel Hill, NC, USA
- 5IRCCS Fondazione Santa Lucia, Rome, Italy
- ↵*Corresponding author. Tel: +1 858 646 3161; E‐mail: lpuri{at}sanfordburnham.org
↵† These authors contributed equally to this work
The two catalytic subunits of the SWI/SNF chromatin‐remodeling complex have distinct functions during skeletal muscle differentiation. Brm promotes cell cycle arrest by repressing cyclin D1, controls satellite cell proliferation and activates late muscle genes, while Brg1 activates muscle genes at early stages of myogenesis.
Synopsis
The two catalytic subunits of the SWI/SNF chromatin‐remodeling complex have distinct functions during skeletal muscle differentiation. Brm promotes cell cycle arrest by repressing cyclin D1, controls satellite cell proliferation and activates late muscle genes, while Brg1 activates muscle genes at early stages of myogenesis.
Brm and Brg1 regulate distinct stages of muscle differentiation during skeletal myogenesis.
Brm‐mediated repression of cyclin D1 is required for myoblast cell cycle arrest prior to differentiation.
Brm is required for activation of late muscle differentiation and proper muscle regeneration.
EMBO Reports (2015) 16: 1037–1050
- Received January 27, 2015.
- Revision received May 21, 2015.
- Accepted May 25, 2015.
- © 2015 The Authors
- Transcription factor p63 bookmarks and regulates dynamic enhancers during epidermal differentiation
- Evelyn N Kouwenhoven1,2,
- Martin Oti2,
- Hanna Niehues3,
- Simon J van Heeringen2,
- Joost Schalkwijk3,
- Hendrik G Stunnenberg4,
- Hans van Bokhoven1 and
- Huiqing Zhou*,1,2
- 1Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
- 2Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences Radboud University, Nijmegen, The Netherlands
- 3Department of Dermatology, Radboud Institute for Molecular Life Sciences Radboud University Medical Center, Nijmegen, The Netherlands
- 4Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences Radboud University, Nijmegen, The Netherlands
- ↵*Corresponding author. Tel: +31 24 3616851; E‐mail: jo.zhou{at}radboudumc.nl; j.zhou{at}science.ru.nl
The key epithelial transcription factor p63 functions as a placeholder to bookmark genomic loci for gene regulation in epithelial development. The data suggest that different sets of co‐regulators are required to activate proliferation and differentiation genes during epidermal differentiation and developmental genes in other epithelial tissues.
Synopsis
The key epithelial transcription factor p63 functions as a placeholder to bookmark genomic loci for gene regulation in epithelial development. The data suggest that different sets of co‐regulators are required to activate proliferation and differentiation genes during epidermal differentiation and developmental genes in other epithelial tissues.
We report p63‐regulated gene expression dynamics during epidermal differentiation.
Gene expression correlates with the activity of p63‐dependent enhancers rather than p63 binding itself.
Co‐regulators of p63 are required during epidermal differentiation and the development of other epithelial tissues.
EMBO Reports (2015) 16: 863–878
- Received December 2, 2014.
- Revision received March 11, 2015.
- Accepted April 20, 2015.
- © 2015 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
- Paternal H3K4 methylation is required for minor zygotic gene activation and early mouse embryonic development
- 1Laboratory of Pathology and Development, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo‐ku Tokyo, Japan
- 2Division of Molecular Pathobiology, Center for Zoonosis Control, Hokkaido University, Kita‐ku Sapporo, Japan
- 3Research Fellow of Japan Society for the Promotion of Science, Chiyoda‐ku Tokyo, Japan
- 4PRESTO, Japan Science and Technology Agency (JST), Kawaguchi‐Honcho Saitama, Japan
- ↵*Corresponding author. Tel: +81 3 5841 7831; E‐mail: ytokada{at}iam.u-tokyo.ac.jp
In the mouse zygote, transcriptional properties are asymmetric between male and female pronuclei. This study shows that in the male pronucleus, minor zygotic gene activation requires Mll3/4‐dependent H3K4 monomethylation likely at enhancers.
Synopsis
In the mouse zygote, transcriptional properties are asymmetric between male and female pronuclei. This study shows that in the male pronucleus, minor zygotic gene activation requires Mll3/4‐dependent H3K4 monomethylation likely at enhancers.
Overexpression of H3.3 K4M mutant in the zygote causes global reduction of paternal H3K4 methylation, minor zygotic transcription, and subsequent embryonic development.
Mll3/4, responsible enzymes for H3K4 monomethylation at enhancer regions, are involved in paternal minor ZGA.
EMBO Reports (2015) 16: 803–812
- Received October 9, 2014.
- Revision received April 4, 2015.
- Accepted April 9, 2015.
- © 2015 The Authors
- Induction of hematopoietic and endothelial cell program orchestrated by ETS transcription factor ER71/ETV2
- Fang Liu1,
- Daofeng Li2,
- Yik Yeung Lawrence Yu1,
- Inyoung Kang1,
- Min‐Ji Cha16,
- Ju Young Kim3,
- Changwon Park3,
- Dennis K Watson4,
- Ting Wang*,2 and
- Kyunghee Choi*,1,5
- 1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
- 2Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA
- 3Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA, USA
- 4Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA
- 5Developmental, Regenerative, and Stem Cell Biology Program, Washington University School of Medicine, St. Louis, MO, USA
- 6Catholic Kwandong University, Institute for Bio‐Medical Convergence, College of Medicine, Korea
- ↵*
Corresponding author. Tel: +1 3142 860865; E‐mail: twang{at}genetics.wustl.edu
Corresponding author. Tel: +1 3143 628716; E‐mail: kchoi{at}wustl.edu
ETV2 controls the gene regulatory network and signaling involved in the hemangiogenic progenitor specification from mesoderm.
Synopsis
ETV2 controls the gene regulatory network and signaling involved in the hemangiogenic progenitor specification from mesoderm.
ETV2 induces key genes regulating hematopoietic and endothelial cell lineage specification.
ETV2 function is specifically required for the generation of the FLK1highPDGFRα− cell population.
ETV2 induces other Ets genes, which subsequently maintain ETV2‐initiated blood and endothelial cell programs through an ETS switching mechanism.
EMBO Reports (2015) 16: 654–669
- Received December 2, 2014.
- Revision received February 24, 2015.
- Accepted February 26, 2015.
- © 2015 The Authors
- Stella preserves maternal chromosome integrity by inhibiting 5hmC‐induced γH2AX accumulation
- Tsunetoshi Nakatani1,
- Kazuo Yamagata2,
- Tohru Kimura1,3,4,
- Masaaki Oda1,3,
- Hiroyuki Nakashima3,
- Mayuko Hori2,
- Yoichi Sekita1,4,
- Tatsuhiko Arakawa3,
- Toshinobu Nakamura5,6 and
- Toru Nakano*,1,3,6
- 1Department of Pathology, Medical School, Osaka University, Osaka, Japan
- 2Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
- 3Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
- 4Kitasato University School of Science, Kanagawa, Japan
- 5Nagahama Institute of Bio‐Science and Technology, Shiga, Japan
- 6Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan
- ↵*Corresponding author. Tel: +81 6 6879 3720, 3722; Fax: +81 6 6879 3729; E‐mail: tnakano{at}patho.med.osaka-u.ac.jp
Loss of Stella results in Tet3‐induced γH2AX accumulation in maternal chromatin, the formation of ectopic micronuclei, and delay of DNA replication in mouse zygotes.
Synopsis
Loss of Stella results in Tet3‐induced γH2AX accumulation in maternal chromatin, the formation of ectopic micronuclei, and delay of DNA replication in mouse zygotes.
Stella‐null embryos show ectopic micronuclei from maternal chromatin and impaired DNA replication.
Maternal chromatin in Stella‐null embryos accumulates aberrant γH2AX.
Tet3 induces γH2AX accumulation in vivo and in vitro and impairment of DNA replication and cell growth in vitro.
EMBO Reports (2015) 16: 582–589
- Received August 7, 2014.
- Revision received January 22, 2015.
- Accepted January 26, 2015.
- © 2015 The Authors
- Intellectual disability‐associated dBRWD3 regulates gene expression through inhibition of HIRA/YEM‐mediated chromatin deposition of histone H3.3
- Wei‐Yu Chen1,†,
- Hsueh‐Tzu Shih1,†,
- Kuei‐Yan Liu1,
- Zong‐Siou Shih1,
- Li‐Kai Chen1,
- Tsung‐Han Tsai1,
- Mei‐Ju Chen2,
- Hsuan Liu3,4,
- Bertrand Chin‐Ming Tan4,5,
- Chien‐Yu Chen6,
- Hsiu‐Hsiang Lee1,
- Benjamin Loppin7,
- Ounissa Aït‐Ahmed8 and
- June‐Tai Wu*,1,9,10
- 1Institute of Molecular Medicine College of Medicine National Taiwan University, Taipei, Taiwan
- 2Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei, Taiwan
- 3Department of Cell and Molecular Biology, College of Medicine Chang Gung University, Tao‐Yuan, Taiwan
- 4Molecular Medicine Research Center Chang Gung University, Tao‐Yuan, Taiwan
- 5Department of Biomedical Sciences and Graduate Institute of Biomedical Sciences, College of Medicine Chang Gung University, Tao‐Yuan, Taiwan
- 6Bio‐Industrial Mechatronics Engineering, National Taiwan University, Taipei, Taiwan
- 7Centre de Génétique et de Physiologie Moléculaire et Cellulaire CNRS UMR5534 Université Claude Bernard Lyon 1, Villeurbanne, France
- 8Institute of Regenerative medicine and Biotherapy (IRMB) Inserm U1203 Saint‐Eloi Hospital, CHRU Montpellier, France
- 9Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- 10Research Center for Developmental Biology and Regenerative Medicine National Taiwan University, Taipei, Taiwan
- ↵*Corresponding author. Tel: +886 2 23123456 ext 88367; E‐mail: junetai.wu{at}gmail.com
-
↵† These authors contributed equally to this work
BRWD3 is mutated in patients with X‐linked intellectual disability. Here, dBRWD3 is found to negatively regulate the amount of chromatin‐associated H3.3, thereby regulating gene expression in the brain and several developmental processes.
Synopsis
BRWD3 is mutated in patients with X‐linked intellectual disability. Here, dBRWD3 is found to negatively regulate the amount of chromatin‐associated H3.3, thereby regulating gene expression in the brain and several developmental processes.
dBRWD3 mutation causes various developmental abnormalities by altering gene expression.
HIRA/YEM‐mediated H3.3 deposition is increased in dBRWD3 mutants.
The transcriptomic changes and diverse developmental defects of dBRWD3 mutants are suppressed by inactivation of the HIRA/YEM–H3.3 pathway.
EMBO Reports (2015) 16: 528–538
- Received May 23, 2014.
- Revision received January 15, 2015.
- Accepted January 16, 2015.
- © 2015 The Authors
- Glycolytic enzymes localize to ribonucleoprotein granules in Drosophila germ cells, bind Tudor and protect from transposable elements
- Ming Gao1,†,
- Travis C Thomson2,†,
- T Michael Creed1,
- Shikui Tu3,
- Sudan N Loganathan1,
- Christina A Jackson1,
- Patrick McCluskey1,
- Yanyan Lin1,
- Scott E Collier4,
- Zhiping Weng3,
- Paul Lasko5,
- Melanie D Ohi4 and
- Alexey L Arkov*,1
- 1Department of Biological Sciences, Murray State University, Murray, KY, USA
- 2Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA
- 3Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA, USA
- 4Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA
- 5Department of Biology, McGill University, Montreal, QC, Canada
- ↵*Corresponding author. Tel: +1 270 809 6053; E‐mail: aarkov{at}murraystate.edu
-
↵† Co‐first authors
Glycolytic enzymes localize to ribonucleoprotein granules in Drosophila germ cells, the genomes of which they protect from the expression of transposable elements. The enzymes also associate with the germ granule Tudor protein.
Synopsis
Glycolytic enzymes localize to ribonucleoprotein granules in Drosophila germ cells, the genomes of which they protect from the expression of transposable elements. The enzymes also associate with the germ granule Tudor protein.
Glycolytic enzymes localize to ribonucleoprotein granules in germ cells and protect the germline from transposable elements.
In granules, ATP‐producing glycolytic enzymes are located in the vicinity of ATP‐dependent RNA helicases.
The first EM structure of the full‐length Tudor protein and its binding to glycolytic enzymes are reported.
EMBO Reports (2015) 16: 379–386
- Received October 6, 2014.
- Revision received December 2, 2014.
- Accepted December 9, 2014.
- © 2015 The Authors
- Cabut/dTIEG associates with the transcription factor Yorkie for growth control
- Marina Ruiz‐Romero1,
- Enrique Blanco1,2,
- Nuria Paricio3,
- Florenci Serras1 and
- Montserrat Corominas*,1
- 1Departament de Genètica, Facultat de Biologia and Institut de Biomedicina (IBUB) de la Universitat de Barcelona, Barcelona, Spain
- 2Centre for Genomic Regulation (CRG), Barcelona, Spain
- 3Departamento de Genética, Facultad de Ciencias Biológicas, Universidad de Valencia, Valencia, Spain
- ↵*Corresponding author. Tel: +34 93 4037003; E‐mail: mcorominas{at}ub.edu
The transcription factor Cbt associates with Yki, a key effector of growth control in the Hippo pathway. Up‐regulation of Cbt promotes cell proliferation, while down‐regulation suppresses Yki‐dependent overgrowth in Drosophila.
Synopsis
The transcription factor Cbt associates with Yki, a key effector of growth control in the Hippo pathway. Up‐regulation of Cbt promotes cell proliferation, while down‐regulation suppresses Yki‐dependent overgrowth in Drosophila.
Cbt co‐localizes with Yki on common gene promoters.
Cbt is required for Yki activity in wing and eye development.
Cbt acts as a modulator of Yki activity in tissue growth control.
EMBO Reports (2015) 16: 362–369
- Received June 20, 2014.
- Revision received November 24, 2014.
- Accepted December 8, 2014.
- © 2015 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
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