Two independent transcription initiation codes overlap on vertebrate core promoters

• Published in: Nature (London) 2014-03, Vol.507 (7492), p.381-385
• Main Authors: 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, Strähle, Uwe, Carninci, Piero, Müller, Ferenc, Lenhard, Boris
• Format: Article
• Language: English
• Subjects: 38/15; 38/39; 42/35; 42/44; 631/114; 631/136/1455; 631/337/100/1701; 631/337/2019; 64/116; Analysis; Animals; Base Sequence; Deoxyribonucleic acid; DNA; Embryo, Nonmammalian - embryology; Embryo, Nonmammalian - metabolism; Embryonic growth stage; Embryos; Female; Gene expression; Gene Expression Regulation, Developmental - genetics; Genetic aspects; Genetic code; Genetic research; Genetic transcription; Histones - metabolism; Humanities and Social Sciences; letter; Methylation; Mothers; multidisciplinary; Nucleosomes - genetics; Promoter Regions, Genetic - genetics; Promoters (Genetics); Science; Transcription Initiation Site; Transcription Initiation, Genetic; Transcriptome - genetics; Vertebrates; Zebra fish; Zebrafish - embryology; Zebrafish - genetics; Zygote - metabolism; Zygotes
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature12974

The transcription start sites used during the maternal to zygotic transition in zebrafish are mapped, revealing that the transition is characterized by a switch between two different sequence signs to guide transcription initiation, which often co-exist in core promoters. A fresh start for zygotic transcription The maternal-to-zygotic transition (MZT) during vertebrate embryogenesis represents a dramatic change of the transcriptome, when the zygotic genome is activated and maternal transcripts are degraded. This study maps the transcription start sites used during MZT in zebrafish at nucleotide resolution, and shows that the transition from maternal to zygotic transcriptome is characterized by a switch between two different promoter sequence signals. The position at which RNA transcription starts is determined by an A/T-rich motif at the maternal stage and by fundamentally different codes in the zygote. The two transcription start sites often coexist — and may even overlap — in core promoters and are differentially utilized at promoters active in both oocyte and embryo. A core promoter is a stretch of DNA surrounding the transcription start site (TSS) that integrates regulatory inputs 1 and recruits general transcription factors to initiate transcription 2 . 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 3 , 4 , 5 , 6 . 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 7 . 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 8 , and determined the positions of H3K4me3-marked promoter-associated nucleosomes 9 . 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 s