This Article Full Text Full Text (PDF) Supplemental Research Data All Versions of this Article: gr.4222606v1 16/1/1    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cooper, S. J. Articles by Myers, R. M. Search for Related Content PubMed PubMed Citation Articles by Cooper, S. J. Articles by Myers, R. M. Social Bookmarking                   What's this?

Comprehensive analysis of transcriptional promoter structure and function in 1% of the human genome

Department of Genetics, Stanford University School of Medicine, Stanford, California 94305-5120, USA

Transcriptional promoters comprise one of many classes of eukaryotic transcriptional regulatory elements. Identification and characterization of these elements are vital to understanding the complex network of human gene regulation. Using full-length cDNA sequences to identify transcription start sites (TSS), we predicted more than 900 putative human transcriptional promoters in the ENCODE regions, representing a comprehensive sampling of promoters in 1% of the genome. We identified 387 fragments that function as promoters in at least one of 16 cell lines by measuring promoter activity in high-throughput transient transfection reporter assays. These positive functional results demonstrate widespread use of alternative promoters. We show a strong correlation between promoter activity and the corresponding endogenous RNA transcript levels, providing the first experimental quantitative estimate of promoter contribution to gene regulation. Finally, we identified functional regions within a randomly selected subset of 45 promoters using deletion analyses. These experiments showed that, on average, the sequence -300 to -50 bp of the TSS positively contributes to core promoter activity. Interestingly, putative negative elements were identified -1000 to -500 bp upstream of the TSS for 55% of genes tested. These data provide the largest and most comprehensive view of promoter function in the human genome.

¹ Corresponding author.
E-mail nathant{at}stanford.edu; fax (650) 725-9689.

[Supplemental material is available online at www.genome.org.]

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. S. Johnson, W. Li, D. B. Gordon, A. Bhattacharjee, B. Curry, J. Ghosh, L. Brizuela, J. S. Carroll, M. Brown, P. Flicek, et al. Systematic evaluation of variability in ChIP-chip experiments using predefined DNA targets Genome Res., March 1, 2008; 18(3): 393 - 403. [Abstract] [Full Text] [PDF]

				T. Abeel, Y. Saeys, E. Bonnet, P. Rouze, and Y. Van de Peer Generic eukaryotic core promoter prediction using structural features of DNA Genome Res., February 1, 2008; 18(2): 310 - 323. [Abstract] [Full Text] [PDF]

				M. C. Frith, E. Valen, A. Krogh, Y. Hayashizaki, P. Carninci, and A. Sandelin A code for transcription initiation in mammalian genomes Genome Res., January 1, 2008; 18(1): 1 - 12. [Abstract] [Full Text] [PDF]

				A. Chabot, R. A. Shrit, R. Blekhman, and Y. Gilad Using Reporter Gene Assays to Identify cis Regulatory Differences Between Humans and Chimpanzees Genetics, August 1, 2007; 176(4): 2069 - 2076. [Abstract] [Full Text] [PDF]

				N. D. Trinklein, U. Karaoz, J. Wu, A. Halees, S. Force Aldred, P. J. Collins, D. Zheng, Z. D. Zhang, M. B. Gerstein, M. Snyder, et al. Integrated analysis of experimental data sets reveals many novel promoters in 1% of the human genome Genome Res., June 1, 2007; 17(6): 720 - 731. [Abstract] [Full Text] [PDF]

				D. C. King, J. Taylor, Y. Zhang, Y. Cheng, H. A. Lawson, J. Martin, ENCODE groups for Transcriptional Regulation and M, F. Chiaromonte, W. Miller, and R. C. Hardison Finding cis-regulatory elements using comparative genomics: Some lessons from ENCODE data Genome Res., June 1, 2007; 17(6): 775 - 786. [Abstract] [Full Text] [PDF]

				P. G. Giresi, J. Kim, R. M. McDaniell, V. R. Iyer, and J. D. Lieb FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin Genome Res., June 1, 2007; 17(6): 877 - 885. [Abstract] [Full Text] [PDF]

				F. Muller, M. A. Demeny, and L. Tora New Problems in RNA Polymerase II Transcription Initiation: Matching the Diversity of Core Promoters with a Variety of Promoter Recognition Factors J. Biol. Chem., May 18, 2007; 282(20): 14685 - 14689. [Full Text] [PDF]

				J. Ponjavic, C. P. Ponting, and G. Lunter Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs Genome Res., May 1, 2007; 17(5): 556 - 565. [Abstract] [Full Text] [PDF]

				A. L. Hancock, K. W. Brown, K. Moorwood, H. Moon, C. Holmgren, S. H. Mardikar, A. R. Dallosso, E. Klenova, D. Loukinov, R. Ohlsson, et al. A CTCF-binding silencer regulates the imprinted genes AWT1 and WT1-AS and exhibits sequential epigenetic defects during Wilms' tumourigenesis Hum. Mol. Genet., February 1, 2007; 16(3): 343 - 354. [Abstract] [Full Text] [PDF]

				D. Baek, C. Davis, B. Ewing, D. Gordon, and P. Green Characterization and predictive discovery of evolutionarily conserved mammalian alternative promoters Genome Res., February 1, 2007; 17(2): 145 - 155. [Abstract] [Full Text] [PDF]

				L. Elnitski, V. X. Jin, P. J. Farnham, and S. J.M. Jones Locating mammalian transcription factor binding sites: A survey of computational and experimental techniques Genome Res., December 1, 2006; 16(12): 1455 - 1464. [Abstract] [Full Text] [PDF]

				J. Taylor, S. Tyekucheva, D. C. King, R. C. Hardison, W. Miller, and F. Chiaromonte ESPERR: Learning strong and weak signals in genomic sequence alignments to identify functional elements Genome Res., December 1, 2006; 16(12): 1596 - 1604. [Abstract] [Full Text] [PDF]

				A. J.M. Walhout Unraveling transcription regulatory networks by protein-DNA and protein-protein interaction mapping Genome Res., December 1, 2006; 16(12): 1445 - 1454. [Abstract] [Full Text] [PDF]

				T. Pastinen, B. Ge, and T. J. Hudson Influence of human genome polymorphism on gene expression. Hum. Mol. Genet., April 15, 2006; 15(suppl_1): R9 - R16. [Abstract] [Full Text] [PDF]