Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis
Abstract Background The work of the FANTOM5 Consortium has brought forth a new level of understanding of the regulation of gene transcription and the cellular processes involved in creating diversity of cell types. In this study, we extended the analysis of the FANTOM5 Cap Analysis of Gene Expressio...
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2019-09-01
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| Series: | BMC Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12864-019-6063-9 |
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doaj-26886484d3af4071954fe82631526e362020-11-25T01:29:01ZengBMCBMC Genomics1471-21642019-09-0120111710.1186/s12864-019-6063-9Identification of novel cerebellar developmental transcriptional regulators with motif activity analysisThomas J. Ha0Peter G. Y. Zhang1Remi Robert2Joanna Yeung3Douglas J. Swanson4Anthony Mathelier5Wyeth W. Wasserman6Sujin Im7Masayoshi Itoh8Hideya Kawaji9Timo Lassmann10Carsten O. Daub11Erik Arner12The FANTOM Consortium13Piero Carninci14Yoshihide Hayashizaki15Alistair R. R. Forrest16Daniel Goldowitz17Centre for Molecular Medicine and Therapeutics at the BC Children’s Hospital Research Institute, Department of Medical Genetics, University of British ColumbiaCentre for Molecular Medicine and Therapeutics at the BC Children’s Hospital Research Institute, Department of Medical Genetics, University of British ColumbiaCentre for Molecular Medicine and Therapeutics at the BC Children’s Hospital Research Institute, Department of Medical Genetics, University of British ColumbiaCentre for Molecular Medicine and Therapeutics at the BC Children’s Hospital Research Institute, Department of Medical Genetics, University of British ColumbiaCentre for Molecular Medicine and Therapeutics at the BC Children’s Hospital Research Institute, Department of Medical Genetics, University of British ColumbiaCentre for Molecular Medicine and Therapeutics at the BC Children’s Hospital Research Institute, Department of Medical Genetics, University of British ColumbiaCentre for Molecular Medicine and Therapeutics at the BC Children’s Hospital Research Institute, Department of Medical Genetics, University of British ColumbiaCentre for Molecular Medicine and Therapeutics at the BC Children’s Hospital Research Institute, Department of Medical Genetics, University of British ColumbiaRIKEN Omics Science Center (OSC)RIKEN Omics Science Center (OSC)RIKEN Omics Science Center (OSC)RIKEN Omics Science Center (OSC)RIKEN Omics Science Center (OSC)RIKEN Omics Science Center (OSC)RIKEN Omics Science Center (OSC)RIKEN Omics Science Center (OSC)RIKEN Omics Science Center (OSC)Centre for Molecular Medicine and Therapeutics at the BC Children’s Hospital Research Institute, Department of Medical Genetics, University of British ColumbiaAbstract Background The work of the FANTOM5 Consortium has brought forth a new level of understanding of the regulation of gene transcription and the cellular processes involved in creating diversity of cell types. In this study, we extended the analysis of the FANTOM5 Cap Analysis of Gene Expression (CAGE) transcriptome data to focus on understanding the genetic regulators involved in mouse cerebellar development. Results We used the HeliScopeCAGE library sequencing on cerebellar samples over 8 embryonic and 4 early postnatal times. This study showcases temporal expression pattern changes during cerebellar development. Through a bioinformatics analysis that focused on transcription factors, their promoters and binding sites, we identified genes that appear as strong candidates for involvement in cerebellar development. We selected several candidate transcriptional regulators for validation experiments including qRT-PCR and shRNA transcript knockdown. We observed marked and reproducible developmental defects in Atf4, Rfx3, and Scrt2 knockdown embryos, which support the role of these genes in cerebellar development. Conclusions The successful identification of these novel gene regulators in cerebellar development demonstrates that the FANTOM5 cerebellum time series is a high-quality transcriptome database for functional investigation of gene regulatory networks in cerebellar development.http://link.springer.com/article/10.1186/s12864-019-6063-9Cerebellar developmentTranscriptomeHeliScopeCAGEMotif activityTransfactivityTranscription factors |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Thomas J. Ha Peter G. Y. Zhang Remi Robert Joanna Yeung Douglas J. Swanson Anthony Mathelier Wyeth W. Wasserman Sujin Im Masayoshi Itoh Hideya Kawaji Timo Lassmann Carsten O. Daub Erik Arner The FANTOM Consortium Piero Carninci Yoshihide Hayashizaki Alistair R. R. Forrest Daniel Goldowitz |
| spellingShingle |
Thomas J. Ha Peter G. Y. Zhang Remi Robert Joanna Yeung Douglas J. Swanson Anthony Mathelier Wyeth W. Wasserman Sujin Im Masayoshi Itoh Hideya Kawaji Timo Lassmann Carsten O. Daub Erik Arner The FANTOM Consortium Piero Carninci Yoshihide Hayashizaki Alistair R. R. Forrest Daniel Goldowitz Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis BMC Genomics Cerebellar development Transcriptome HeliScopeCAGE Motif activity Transfactivity Transcription factors |
| author_facet |
Thomas J. Ha Peter G. Y. Zhang Remi Robert Joanna Yeung Douglas J. Swanson Anthony Mathelier Wyeth W. Wasserman Sujin Im Masayoshi Itoh Hideya Kawaji Timo Lassmann Carsten O. Daub Erik Arner The FANTOM Consortium Piero Carninci Yoshihide Hayashizaki Alistair R. R. Forrest Daniel Goldowitz |
| author_sort |
Thomas J. Ha |
| title |
Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis |
| title_short |
Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis |
| title_full |
Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis |
| title_fullStr |
Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis |
| title_full_unstemmed |
Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis |
| title_sort |
identification of novel cerebellar developmental transcriptional regulators with motif activity analysis |
| publisher |
BMC |
| series |
BMC Genomics |
| issn |
1471-2164 |
| publishDate |
2019-09-01 |
| description |
Abstract Background The work of the FANTOM5 Consortium has brought forth a new level of understanding of the regulation of gene transcription and the cellular processes involved in creating diversity of cell types. In this study, we extended the analysis of the FANTOM5 Cap Analysis of Gene Expression (CAGE) transcriptome data to focus on understanding the genetic regulators involved in mouse cerebellar development. Results We used the HeliScopeCAGE library sequencing on cerebellar samples over 8 embryonic and 4 early postnatal times. This study showcases temporal expression pattern changes during cerebellar development. Through a bioinformatics analysis that focused on transcription factors, their promoters and binding sites, we identified genes that appear as strong candidates for involvement in cerebellar development. We selected several candidate transcriptional regulators for validation experiments including qRT-PCR and shRNA transcript knockdown. We observed marked and reproducible developmental defects in Atf4, Rfx3, and Scrt2 knockdown embryos, which support the role of these genes in cerebellar development. Conclusions The successful identification of these novel gene regulators in cerebellar development demonstrates that the FANTOM5 cerebellum time series is a high-quality transcriptome database for functional investigation of gene regulatory networks in cerebellar development. |
| topic |
Cerebellar development Transcriptome HeliScopeCAGE Motif activity Transfactivity Transcription factors |
| url |
http://link.springer.com/article/10.1186/s12864-019-6063-9 |
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