CAGE-defined promoter regions of the genes implicated in Rett Syndrome

BMC Genomics

Alka Saxena¹  Piero Carninci⁵  Alistair RR Forrest⁵  Michela Fagiolini⁷  Annarita Patrizi⁷  Peter Zhang⁹  Thomas Ha⁹  Dan Goldowitz⁹  Peter Heutink⁵  Albin Sandelin²  Timo Lassmann⁶  Hideya Kawaji⁴  Leonard Lipovich⁸  Robin Andersson²  Nicolas Bertin³  Morana Vitezic² 

[1] Currently at: Biomedical Research Centre at Guy’s and St Thomas’ Trust, Genomics Core Facility, Guy’s Hospital, London, UK;The Bioinformatics Center, Department of Biology and Biotech Research and Innovation Center, University of Copenhagen, Copenhagen, Denmark;Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore;RIKEN Preventive Medicine and Diagnosis Innovation Program (PMI), Wako, Japan;RIKEN Center for Life Science Technologies, Division of Genomic Technologies (DGT), Yokohama, Japan;Telethon Kids Institute, The University of Western Australia, Perth, Australia;FM Kirby Neurobiology Center, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA;Department of Neurology, School of Medicine, Wayne State University, Detroit, MI, USA;Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Dept of Medical Genetics, University of British Columbia, Vancouver, Canada

关键词: Promoter architecture;    Transcriptomics;    CAGE;    Rett Syndrome;   

Others  :  1128412
DOI  :  10.1186/1471-2164-15-1177

 received in 2013-11-17, accepted in 2014-12-04,  发布年份 2014

【 摘 要 】

Background

Mutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other with respect to expression levels and regulatory regions. Here we analyzed data from hundreds of mouse and human samples included in the FANTOM5 project, to identify transcript initiation sites, expression levels, expression correlations and regulatory regions of the three genes.

Results

Our investigations reveal the predominantly used transcription start sites (TSSs) for each gene including novel transcription start sites for FOXG1. We show that FOXG1 expression is poorly correlated with the expression of MECP2 and CDKL5. We identify promoter shapes for each TSS, the predicted location of enhancers for each gene and the common transcription factors likely to regulate the three genes. Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum.

Conclusions

Our analyses provide a comprehensive picture of the regulatory regions of the three genes involved in Rett Syndrome.

【 授权许可】

   
2014 Vitezic et al.; licensee BioMed Central.

【 图 表 】

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