Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis

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, Piero Carninci, Yoshihide Hayashizaki, Alistair R.R. Forrest, Daniel Goldowitz

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Article number718
JournalBMC Genomics
Volume20
Issue number1
DOIs
Publication statusPublished - 18 Sep 2019

Fingerprint

Transcriptome
Genes
Gene Regulatory Networks
Regulator Genes
Computational Biology
Cerebellum
Small Interfering RNA
Libraries
Transcription Factors
Embryonic Structures
Binding Sites
Databases
Gene Expression
Polymerase Chain Reaction

Cite this

Ha, T. J., Zhang, P. G. Y., Robert, R., Yeung, J., Swanson, D. J., Mathelier, A., ... Goldowitz, D. (2019). Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis. BMC Genomics, 20(1), [718]. https://doi.org/10.1186/s12864-019-6063-9
Ha, Thomas J. ; Zhang, Peter G.Y. ; Robert, Remi ; Yeung, Joanna ; Swanson, Douglas J. ; Mathelier, Anthony ; Wasserman, Wyeth W. ; Im, Sujin ; Itoh, Masayoshi ; Kawaji, Hideya ; Lassmann, Timo ; Daub, Carsten O. ; Arner, Erik ; Carninci, Piero ; Hayashizaki, Yoshihide ; Forrest, Alistair R.R. ; Goldowitz, Daniel. / Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis. In: BMC Genomics. 2019 ; Vol. 20, No. 1.
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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.",
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Ha, TJ, Zhang, PGY, Robert, R, Yeung, J, Swanson, DJ, Mathelier, A, Wasserman, WW, Im, S, Itoh, M, Kawaji, H, Lassmann, T, Daub, CO, Arner, E, Carninci, P, Hayashizaki, Y, Forrest, ARR & Goldowitz, D 2019, 'Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis' BMC Genomics, vol. 20, no. 1, 718. https://doi.org/10.1186/s12864-019-6063-9

Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis. / Ha, Thomas J.; Zhang, Peter G.Y.; Robert, Remi; Yeung, Joanna; Swanson, Douglas J.; Mathelier, Anthony; Wasserman, Wyeth W.; Im, Sujin; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Daub, Carsten O.; Arner, Erik; Carninci, Piero; Hayashizaki, Yoshihide; Forrest, Alistair R.R.; Goldowitz, Daniel.

In: BMC Genomics, Vol. 20, No. 1, 718, 18.09.2019.

Research output: Contribution to journalArticle

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T1 - Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis

AU - Ha, Thomas J.

AU - Zhang, Peter G.Y.

AU - Robert, Remi

AU - Yeung, Joanna

AU - Swanson, Douglas J.

AU - Mathelier, Anthony

AU - Wasserman, Wyeth W.

AU - Im, Sujin

AU - Itoh, Masayoshi

AU - Kawaji, Hideya

AU - Lassmann, Timo

AU - Daub, Carsten O.

AU - Arner, Erik

AU - Carninci, Piero

AU - Hayashizaki, Yoshihide

AU - Forrest, Alistair R.R.

AU - Goldowitz, Daniel

PY - 2019/9/18

Y1 - 2019/9/18

N2 - 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.

AB - 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.

KW - Atf4

KW - Cerebellar development

KW - HeliScopeCAGE

KW - Motif activity

KW - Rfx3

KW - RNAi

KW - Scrt2

KW - Transcription factors

KW - Transcriptome

KW - Transfactivity

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