Dynamic usage of transcription start sites within core promoters

BackgroundMammalian promoters do not initiate transcription at single, well defined base pairs, but rather at multiple, alternative start sites spread across a region. We previously characterized the static structures of transcription start site usage within promoters at the base pair level, based on large-scale sequencing of transcript 5' ends.ResultsIn the present study we begin to explore the internal dynamics of mammalian promoters, and demonstrate that start site selection within many mouse core promoters varies among tissues. We also show that this dynamic usage of start sites is associated with CpG islands, broad and multimodal promoter structures, and imprinting.ConclusionOur results reveal a new level of biologic complexity within promoters - fine-scale regulation of transcription starting events at the base pair level. These events are likely to be related to epigenetic transcriptional regulation.

[1]  M. Surani,et al.  Epigenetic reprogramming in mouse primordial germ cells , 2002, Mechanisms of Development.

[2]  S. Siegel,et al.  Nonparametric Statistics for the Behavioral Sciences , 2022, The SAGE Encyclopedia of Research Design.

[3]  T. Andrews,et al.  The Ensembl automatic gene annotation system. , 2004, Genome research.

[4]  A. Bird,et al.  Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals , 2003, Nature Genetics.

[5]  E. Davidson,et al.  Gene regulatory networks for development. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Peter A. Jones,et al.  The Role of DNA Methylation in Mammalian Epigenetics , 2001, Science.

[7]  S. Salzberg,et al.  The Transcriptional Landscape of the Mammalian Genome , 2005, Science.

[8]  K. Nakai,et al.  Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. , 2005, Genome research.

[9]  F. P. Villena,et al.  Genome imprinting regulated by the mouse Polycomb group protein Eed , 2003, Nature Genetics.

[10]  K. Robertson DNA methylation and chromatin – unraveling the tangled web , 2002, Oncogene.

[11]  J. Wilkins,et al.  Genomic imprinting and methylation: epigenetic canalization and conflict. , 2005, Trends in genetics : TIG.

[12]  E. Liu,et al.  Gene identification signature (GIS) analysis for transcriptome characterization and genome annotation , 2005, Nature Methods.

[13]  Hong Duan,et al.  Role for DNA methylation in the control of cell type–specific maspin expression , 2002, Nature Genetics.

[14]  Hiroki Nagase,et al.  Association of tissue-specific differentially methylated regions (TDMs) with differential gene expression. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Jun Kawai,et al.  Asb4, Ata3, and Dcn are novel imprinted genes identified by high-throughput screening using RIKEN cDNA microarray. , 2002, Biochemical and biophysical research communications.

[16]  J. T. Kadonaga,et al.  The RNA polymerase II core promoter. , 2003, Annual review of biochemistry.

[17]  Martin S. Taylor,et al.  Genome-wide analysis of mammalian promoter architecture and evolution , 2006, Nature Genetics.

[18]  A. Wolffe,et al.  Epigenetics: regulation through repression. , 1999, Science.

[19]  Terrence S. Furey,et al.  The UCSC Genome Browser Database , 2003, Nucleic Acids Res..

[20]  A. Riggs,et al.  Structure of the imprinted mouse Snrpn gene and establishment of its parental-specific methylation pattern. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[21]  C. Kai,et al.  CAGE: cap analysis of gene expression , 2006, Nature Methods.

[22]  Yoshihide Hayashizaki,et al.  Discovery of imprinted transcripts in the mouse transcriptome using large-scale expression profiling. , 2003, Genome research.

[23]  B. Pugh,et al.  Evidence for Functional Binding and Stable Sliding of the TATA Binding Protein on Nonspecific DNA (*) , 1995, The Journal of Biological Chemistry.

[24]  Piero Carninci,et al.  Normalization and subtraction of cap-trapper-selected cDNAs to prepare full-length cDNA libraries for rapid discovery of new genes. , 2000, Genome research.

[25]  Piero Carninci,et al.  Tag-based approaches for transcriptome research and genome annotation , 2005, Nature Methods.

[26]  A Suyama,et al.  Diverse transcriptional initiation revealed by fine, large‐scale mapping of mRNA start sites , 2001, EMBO reports.

[27]  R. Tjian,et al.  Transcription regulation and animal diversity , 2003, Nature.

[28]  Tatiana A. Tatusova,et al.  NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins , 2004, Nucleic Acids Res..

[29]  Jun Kawai,et al.  CAGE Basic/Analysis Databases: the CAGE resource for comprehensive promoter analysis , 2005, Nucleic Acids Res..

[30]  A. Giannis,et al.  Epigenetics--an epicenter of gene regulation: histones and histone-modifying enzymes. , 2005, Angewandte Chemie.

[31]  M. Fagiolini,et al.  Targeting a complex transcriptome: the construction of the mouse full-length cDNA encyclopedia. , 2003, Genome research.

[32]  Y. Hayashizaki,et al.  A genomic scanning method for higher organisms using restriction sites as landmarks. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Yoshihide Hayashizaki,et al.  EICO (Expression-based Imprint Candidate Organizer): finding disease-related imprinted genes , 2004, Nucleic Acids Res..

[34]  W. Reik,et al.  Genomic imprinting: parental influence on the genome , 2001, Nature Reviews Genetics.

[35]  J. Kawai,et al.  Cap analysis gene expression for high-throughput analysis of transcriptional starting point and identification of promoter usage , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[36]  R. Tjian,et al.  Diversified transcription initiation complexes expand promoter selectivity and tissue-specific gene expression. , 2003, Genes & development.

[37]  E. Li,et al.  Preference of DNA methyltransferases for CpG islands in mouse embryonic stem cells. , 2004, Genome research.

[38]  W. Reik,et al.  The need for Eed , 2003, Nature Genetics.

[39]  Max Costa,et al.  Epigenetics and the Environment , 2003, Annals of the New York Academy of Sciences.

[40]  Christopher J. Lee,et al.  Genome-wide detection of tissue-specific alternative splicing in the human transcriptome. , 2002, Nucleic acids research.