title: Two independent transcription initiation codes overlap on vertebrate core promoters.
abstract: 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.
authors: Department of Biology, University of Bergen, Thormøhlensgate 53A, N-5008 Bergen, Norway.|Institute of Clinical Sciences and MRC Clinical Sciences Center, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
authors: Vanja
authors: V
authors: Haberle
authors: School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors: Nan
authors: N
authors: Li
authors: School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors: Yavor
authors: Y
authors: Hadzhiev
authors: RIKEN Omics Science Center, Yokohama, Kanagawa, 230-0045 Japan (ceased to exist on 01 April 2013 due to RIKEN reorganisation).|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.
authors: Charles
authors: C
authors: Plessy
authors: Computational Biology Unit, Uni Computing, Uni Research AS, University of Bergen, Thormøhlensgate 55, N-5008 Bergen, Norway.
authors: Christopher
authors: C
authors: Previti
authors: Computational Biology Unit, Uni Computing, Uni Research AS, University of Bergen, Thormøhlensgate 55, N-5008 Bergen, Norway.
authors: Chirag
authors: C
authors: Nepal
authors: School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors: Jochen
authors: J
authors: Gehrig
authors: Computational Biology Unit, Uni Computing, Uni Research AS, University of Bergen, Thormøhlensgate 55, N-5008 Bergen, Norway.
authors: Xianjun
authors: X
authors: Dong
authors: Computational Biology Unit, Uni Computing, Uni Research AS, University of Bergen, Thormøhlensgate 55, N-5008 Bergen, Norway.
authors: Altuna
authors: A
authors: Akalin
authors: RIKEN Omics Science Center, Yokohama, Kanagawa, 230-0045 Japan (ceased to exist on 01 April 2013 due to RIKEN reorganisation).|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.
authors: Ana Maria
authors: AM
authors: Suzuki
authors: Erasmus Medical Center, Center for Biomics, Room Ee679b, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors: Wilfred F J
authors: WFJ
authors: van IJcken
authors: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Postfach 3640, 76021 Karlsruhe, Germany.
authors: Olivier
authors: O
authors: Armant
authors: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Postfach 3640, 76021 Karlsruhe, Germany.
authors: Marco
authors: M
authors: Ferg
authors: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Postfach 3640, 76021 Karlsruhe, Germany.
authors: Uwe
authors: U
authors: Strähle
authors: RIKEN Omics Science Center, Yokohama, Kanagawa, 230-0045 Japan (ceased to exist on 01 April 2013 due to RIKEN reorganisation).|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.
authors: Piero
authors: P
authors: Carninci
authors: School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors: Ferenc
authors: F
authors: Müller
authors: Institute of Clinical Sciences and MRC Clinical Sciences Center, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.|Department of Informatics, University of Bergen, Thormøhlensgate 55, N-5008 Bergen, Norway.
authors: Boris
authors: B
authors: Lenhard
mesh_terms: D000818:Animals; D001483:Base Sequence; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006657:Histones / Q000378:metabolism; D008745:Methylation; D009035:Mothers; D009707:Nucleosomes / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D024363:Transcription Initiation Site; D061785:Transcription Initiation, Genetic; D059467:Transcriptome / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D015053:Zygote / Q000378:metabolism
chemical_list: D006657:Histones; D009707:Nucleosomes