ALBERT

Description: In response to DNA damage, tissue homoeostasis is ensured by protein networks promoting DNA repair, cell cycle arrest or apoptosis. DNA damage response signalling pathways coordinate these processes, partly by propagating gene-expression-modulating signals. DNA damage influences not only the abundance of messenger RNAs, but also their coding information through alternative splicing. Here we show that transcription-blocking DNA lesions promote chromatin displacement of late-stage spliceosomes and initiate a positive feedback loop centred on the signalling kinase ATM. We propose that initial spliceosome displacement and subsequent R-loop formation is triggered by pausing of RNA polymerase at DNA lesions. In turn, R-loops activate ATM, which signals to impede spliceosome organization further and augment ultraviolet-irradiation-triggered alternative splicing at the genome-wide level. Our findings define R-loop-dependent ATM activation by transcription-blocking lesions as an important event in the DNA damage response of non-replicating cells, and highlight a key role for spliceosome displacement in this process.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501432/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501432/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tresini, Maria -- Warmerdam, Daniel O -- Kolovos, Petros -- Snijder, Loes -- Vrouwe, Mischa G -- Demmers, Jeroen A A -- van IJcken, Wilfred F J -- Grosveld, Frank G -- Medema, Rene H -- Hoeijmakers, Jan H J -- Mullenders, Leon H F -- Vermeulen, Wim -- Marteijn, Jurgen A -- 10-0594/Worldwide Cancer Research/United Kingdom -- 233424/European Research Council/International -- 340988/European Research Council/International -- P01 AG017242/AG/NIA NIH HHS/ -- England -- Nature. 2015 Jul 2;523(7558):53-8. doi: 10.1038/nature14512. Epub 2015 Jun 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Cancer Genomics Netherlands, Erasmus University Medical Center, Rotterdam, 3015 CN, The Netherlands. ; Division of Cell Biology, Netherlands Cancer Institute, Amsterdam, 1066 CX, The Netherlands. ; Department of Cell Biology, Erasmus University Medical Center, Rotterdam, 3015 CN, The Netherlands. ; Department of Human Genetics, Leiden University Medical Center, Leiden, 2333 ZC, The Netherlands. ; Erasmus MC Proteomics Center, Erasmus University Medical Center, Rotterdam, 3015 CN, The Netherlands. ; Erasmus Center for Biomics, Erasmus University Medical Center, Rotterdam, 3015 CN, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26106861" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544703/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544703/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van der Lee, Sven J -- Holstege, Henne -- Wong, Tsz Hang -- Jakobsdottir, Johanna -- Bis, Joshua C -- Chouraki, Vincent -- van Rooij, Jeroen G J -- Grove, Megan L -- Smith, Albert V -- Amin, Najaf -- Choi, Seung-Hoan -- Beiser, Alexa S -- Garcia, Melissa E -- van IJcken, Wilfred F J -- Pijnenburg, Yolande A L -- Louwersheimer, Eva -- Brouwer, Rutger W W -- van den Hout, Mirjam C G N -- Oole, Edwin -- Eirkisdottir, Gudny -- Levy, Daniel -- Rotter, Jerome I -- Emilsson, Valur -- O'Donnell, Christopher J -- Aspelund, Thor -- Uitterlinden, Andre G -- Launer, Lenore J -- Hofman, Albert -- Boerwinkle, Eric -- Psaty, Bruce M -- DeStefano, Anita L -- Scheltens, Philip -- Seshadri, Sudha -- van Swieten, John C -- Gudnason, Vilmundur -- van der Flier, Wiesje M -- Ikram, M Arfan -- van Duijn, Cornelia M -- R01 HL105756/HL/NHLBI NIH HHS/ -- UL1 TR000124/TR/NCATS NIH HHS/ -- England -- Nature. 2015 Apr 2;520(7545):E2-3. doi: 10.1038/nature14038.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands. ; 1] Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands [2] Department of Clinical Genetics, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands. ; Department of Neurology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands. ; Icelandic Heart Association, Kopavogur 201, Iceland. ; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98101, USA. ; 1] National Heart, Lung and Blood Institute Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA [2] Boston University School of Medicine, Boston, Massachusetts 02118, USA. ; Department of Internal Medicine, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands. ; School of Public Health, Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA. ; 1] Icelandic Heart Association, Kopavogur 201, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland. ; 1] National Heart, Lung and Blood Institute Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA [2] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. ; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland 20892, USA. ; Center for Biomics, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands. ; Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands. ; 1] National Heart, Lung and Blood Institute Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA [2] Boston University School of Medicine, Boston, Massachusetts 02118, USA [3] National Heart, Lung, and Blood Institute, Intramural Research Program, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA. ; 1] Icelandic Heart Association, Kopavogur 201, Iceland [2] Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik 101, Iceland. ; 1] National Heart, Lung and Blood Institute Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA [2] National Heart, Lung, and Blood Institute, Intramural Research Program, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Icelandic Heart Association, Kopavogur 201, Iceland [2] Centre for Public Health, University of Iceland, Reykjavik 101, Iceland. ; 1] Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [2] Department of Internal Medicine, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [3] Netherlands Consortium on Health Aging and National Genomics Initiative, Leiden 2300 RC, The Netherlands. ; 1] School of Public Health, Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA [2] Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. ; 1] Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98101, USA [2] Department of Epidemiology, University of Washington, Seattle, Washington 98101, USA [3] Group Health Research Institute, Seattle, Washington 98101-1448, USA. ; 1] Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands [2] Department of Neurology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands. ; 1] Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands [2] Department of Epidemiology &Biostatistics, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands. ; 1] Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [2] Department of Neurology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [3] Departments of Radiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25832410" target="_blank"〉PubMed〈/a〉

Description: A core promoter is a stretch of DNA surrounding the transcription start site (TSS) that integrates regulatory inputs and recruits general transcription factors to initiate transcription. The nature and causative relationship of the DNA sequence and chromatin signals that govern the selection of most TSSs by RNA polymerase II remain unresolved. Maternal to zygotic transition represents the most marked change of the transcriptome repertoire in the vertebrate life cycle. Early embryonic development in zebrafish is characterized by a series of transcriptionally silent cell cycles regulated by inherited maternal gene products: zygotic genome activation commences at the tenth cell cycle, marking the mid-blastula transition. This transition provides a unique opportunity to study the rules of TSS selection and the hierarchy of events linking transcription initiation with key chromatin modifications. We analysed TSS usage during zebrafish early embryonic development at high resolution using cap analysis of gene expression, and determined the positions of H3K4me3-marked promoter-associated nucleosomes. Here we show that the transition from the maternal to zygotic transcriptome is characterized by a switch between two fundamentally different modes of defining transcription initiation, which drive the dynamic change of TSS usage and promoter shape. A maternal-specific TSS selection, which requires an A/T-rich (W-box) motif, is replaced with a zygotic TSS selection grammar characterized by broader patterns of dinucleotide enrichments, precisely aligned with the first downstream (+1) nucleosome. The developmental dynamics of the H3K4me3-marked nucleosomes reveal their DNA-sequence-associated positioning at promoters before zygotic transcription and subsequent transcription-independent adjustment to the final position downstream of the zygotic TSS. The two TSS-defining grammars coexist, often physically overlapping, in core promoters of constitutively expressed genes to enable their expression in the two regulatory environments. The dissection of overlapping core promoter determinants represents a framework for future studies of promoter structure and function across different regulatory contexts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haberle, Vanja -- Li, Nan -- Hadzhiev, Yavor -- Plessy, Charles -- Previti, Christopher -- Nepal, Chirag -- Gehrig, Jochen -- Dong, Xianjun -- Akalin, Altuna -- Suzuki, Ana Maria -- van IJcken, Wilfred F J -- Armant, Olivier -- Ferg, Marco -- Strahle, Uwe -- Carninci, Piero -- Muller, Ferenc -- Lenhard, Boris -- MC_UP_1102/1/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2014 Mar 20;507(7492):381-5. doi: 10.1038/nature12974. Epub 2014 Feb 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biology, University of Bergen, Thormohlensgate 53A, N-5008 Bergen, Norway [2] Institute of Clinical Sciences and MRC Clinical Sciences Center, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK [3]. ; 1] School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK [2]. ; School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. ; 1] RIKEN Omics Science Center, Yokohama, Kanagawa 230-0045, Japan [2] RIKEN Center for Life Science Technologies, Division of Genomic Technologies, RIKEN Yokohama Campus, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; 1] Computational Biology Unit, Uni Computing, Uni Research AS, University of Bergen, Thormohlensgate 55, N-5008 Bergen, Norway [2] German Cancer Research Center (DKFZ), Genomics & Proteomics Core Facility (GPCF), Im Neuenheimer Feld 580/TP3, Heidelberg 69120, Germany (C.Pr.); Broegelmann Research Laboratory, The Gade Institute, University of Bergen, The Laboratory Building, Haukeland University Hospital, N-5021 Bergen, Norway (C.N.); Acquifer AG, Sophienstrasse 136, 76135 Karlsruhe, Germany (J.G.); Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA (X.D.); Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland (A.A.). ; 1] School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK [2] German Cancer Research Center (DKFZ), Genomics & Proteomics Core Facility (GPCF), Im Neuenheimer Feld 580/TP3, Heidelberg 69120, Germany (C.Pr.); Broegelmann Research Laboratory, The Gade Institute, University of Bergen, The Laboratory Building, Haukeland University Hospital, N-5021 Bergen, Norway (C.N.); Acquifer AG, Sophienstrasse 136, 76135 Karlsruhe, Germany (J.G.); Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA (X.D.); Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland (A.A.). ; Erasmus Medical Center, Center for Biomics, Room Ee679b, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. ; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Postfach 3640, 76021 Karlsruhe, Germany. ; 1] Institute of Clinical Sciences and MRC Clinical Sciences Center, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK [2] Department of Informatics, University of Bergen, Thormohlensgate 55, N-5008 Bergen, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24531765" target="_blank"〉PubMed〈/a〉