Genome-wide Detection and Analysis of Hippocampus Core Promoters Using DeepCAGE

Overview

Journal Genome Res

Specialty Genetics

Date 2008 Dec 17

PMID 19074369

Citations 89

Authors

Eivind Valen

Giovanni Pascarella

Alistair Chalk

Norihiro Maeda

Miki Kojima

Chika Kawazu

Mitsuyoshi Murata

Hiromi Nishiyori

Dejan Lazarevic

Dario Motti

Troels Torben Marstrand

Man-Hung Eric Tang

Xiaobei Zhao

Anders Krogh

Ole Winther

Takahiro Arakawa

Jun Kawai

Christine Wells

Carsten Daub

Matthias Harbers

Yoshihide Hayashizaki

Stefano Gustincich

Albin Sandelin

Piero Carninci

Affiliations

Soon will be listed here.

Abstract

Finding and characterizing mRNAs, their transcription start sites (TSS), and their associated promoters is a major focus in post-genome biology. Mammalian cells have at least 5-10 magnitudes more TSS than previously believed, and deeper sequencing is necessary to detect all active promoters in a given tissue. Here, we present a new method for high-throughput sequencing of 5' cDNA tags-DeepCAGE: merging the Cap Analysis of Gene Expression method with ultra-high-throughput sequence technology. We apply DeepCAGE to characterize 1.4 million sequenced TSS from mouse hippocampus and reveal a wealth of novel core promoters that are preferentially used in hippocampus: This is the most comprehensive promoter data set for any tissue to date. Using these data, we present evidence indicating a key role for the Arnt2 transcription factor in hippocampus gene regulation. DeepCAGE can also detect promoters used only in a small subset of cells within the complex tissue.

Citing Articles

: a ggplot-based single-gene viewer for visualizing Ribo-seq and related omics datasets.

Wu H, Kaufman I, Hsu P bioRxiv. 2025; .

PMID: 39975054 PMC: 11838514. DOI: 10.1101/2025.01.30.635743.

Classification of Promoter Sequences from Human Genome.

Zaytsev K, Fedorov A, Korotkov E Int J Mol Sci. 2023; 24(16).

PMID: 37628742 PMC: 10454140. DOI: 10.3390/ijms241612561.

Promoter sequence and architecture determine expression variability and confer robustness to genetic variants.

Einarsson H, Salvatore M, Vaagenso C, Alcaraz N, Bornholdt J, Rennie S Elife. 2022; 11.

PMID: 36377861 PMC: 9844987. DOI: 10.7554/eLife.80943.

Database of Potential Promoter Sequences in the Genome.

Rudenko V, Korotkov E Biology (Basel). 2022; 11(8).

PMID: 35892972 PMC: 9332048. DOI: 10.3390/biology11081117.

Synthetic 3'-UTR valves for optimal metabolic flux control in Escherichia coli.

Choe D, Kim K, Kang M, Lee S, Cho S, Palsson B Nucleic Acids Res. 2022; 50(7):4171-4186.

PMID: 35357499 PMC: 9023263. DOI: 10.1093/nar/gkac206.

References

Muller F, Demeny M, Tora L . New problems in RNA polymerase II transcription initiation: matching the diversity of core promoters with a variety of promoter recognition factors. J Biol Chem. 2007; 282(20):14685-9. DOI: 10.1074/jbc.R700012200. View

Janowski B, Huffman K, Schwartz J, Ram R, Hardy D, Shames D . Inhibiting gene expression at transcription start sites in chromosomal DNA with antigene RNAs. Nat Chem Biol. 2006; 1(4):216-22. DOI: 10.1038/nchembio725. View

Sandelin A, Carninci P, Lenhard B, Ponjavic J, Hayashizaki Y, Hume D . Mammalian RNA polymerase II core promoters: insights from genome-wide studies. Nat Rev Genet. 2007; 8(6):424-36. DOI: 10.1038/nrg2026. View

Eisen M, Spellman P, Brown P, Botstein D . Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A. 1998; 95(25):14863-8. PMC: 24541. DOI: 10.1073/pnas.95.25.14863. View

Kodzius R, Kojima M, Nishiyori H, Nakamura M, Fukuda S, Tagami M . CAGE: cap analysis of gene expression. Nat Methods. 2006; 3(3):211-22. DOI: 10.1038/nmeth0306-211. View

Kaur B, Brat D, Devi N, Van Meir E . Vasculostatin, a proteolytic fragment of brain angiogenesis inhibitor 1, is an antiangiogenic and antitumorigenic factor. Oncogene. 2005; 24(22):3632-42. DOI: 10.1038/sj.onc.1208317. View

Kumar P, Wu H, McBride J, Jung K, Kim M, Davidson B . Transvascular delivery of small interfering RNA to the central nervous system. Nature. 2007; 448(7149):39-43. DOI: 10.1038/nature05901. View

Carninci P, Shiraki T, Mizuno Y, Muramatsu M, Hayashizaki Y . Extra-long first-strand cDNA synthesis. Biotechniques. 2002; 32(5):984-5. DOI: 10.2144/02325bm01. View

Ma Q . Transcriptional regulation of neuronal phenotype in mammals. J Physiol. 2006; 575(Pt 2):379-87. PMC: 1819468. DOI: 10.1113/jphysiol.2006.113449. View

10.

Bird C, Burgess N . The hippocampus and memory: insights from spatial processing. Nat Rev Neurosci. 2008; 9(3):182-94. DOI: 10.1038/nrn2335. View

11.

Mercer T, Dinger M, Sunkin S, Mehler M, Mattick J . Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci U S A. 2008; 105(2):716-21. PMC: 2206602. DOI: 10.1073/pnas.0706729105. View

12.

Birney E, Stamatoyannopoulos J, Dutta A, Guigo R, Gingeras T, Margulies E . Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007; 447(7146):799-816. PMC: 2212820. DOI: 10.1038/nature05874. View

13.

Vlieghe D, Sandelin A, De Bleser P, Vleminckx K, Wasserman W, van Roy F . A new generation of JASPAR, the open-access repository for transcription factor binding site profiles. Nucleic Acids Res. 2005; 34(Database issue):D95-7. PMC: 1347477. DOI: 10.1093/nar/gkj115. View

14.

Lein E, Hawrylycz M, Ao N, Ayres M, Bensinger A, Bernard A . Genome-wide atlas of gene expression in the adult mouse brain. Nature. 2006; 445(7124):168-76. DOI: 10.1038/nature05453. View

15.

Sugino K, Hempel C, Miller M, Hattox A, Shapiro P, Wu C . Molecular taxonomy of major neuronal classes in the adult mouse forebrain. Nat Neurosci. 2005; 9(1):99-107. DOI: 10.1038/nn1618. View

16.

Kawaji H, Frith M, Katayama S, Sandelin A, Kai C, Kawai J . Dynamic usage of transcription start sites within core promoters. Genome Biol. 2006; 7(12):R118. PMC: 1794431. DOI: 10.1186/gb-2006-7-12-r118. View

17.

Wasserman W, Sandelin A . Applied bioinformatics for the identification of regulatory elements. Nat Rev Genet. 2004; 5(4):276-87. DOI: 10.1038/nrg1315. View

18.

Nakazawa K, McHugh T, Wilson M, Tonegawa S . NMDA receptors, place cells and hippocampal spatial memory. Nat Rev Neurosci. 2004; 5(5):361-72. DOI: 10.1038/nrn1385. View

19.

Kanamori M, Konno H, Osato N, Kawai J, Hayashizaki Y, Suzuki H . A genome-wide and nonredundant mouse transcription factor database. Biochem Biophys Res Commun. 2004; 322(3):787-93. DOI: 10.1016/j.bbrc.2004.07.179. View

20.

Carninci P, Kasukawa T, Katayama S, Gough J, Frith M, Maeda N . The transcriptional landscape of the mammalian genome. Science. 2005; 309(5740):1559-63. DOI: 10.1126/science.1112014. View