Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis.
Activating Transcription Factor 4
/ deficiency
Animals
Cerebellum
/ embryology
Gene Expression Profiling
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Mice
Mice, Inbred C57BL
Nucleotide Motifs
/ genetics
Promoter Regions, Genetic
/ genetics
Regulatory Factor X Transcription Factors
/ deficiency
Transcription Factors
/ deficiency
Transcription, Genetic
/ genetics
Atf4
Cerebellar development
HeliScopeCAGE
Motif activity
RNAi
Rfx3
Scrt2
Transcription factors
Transcriptome
Transfactivity
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
18 Sep 2019
18 Sep 2019
Historique:
received:
02
10
2018
accepted:
26
08
2019
entrez:
20
9
2019
pubmed:
20
9
2019
medline:
28
1
2020
Statut:
epublish
Résumé
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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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.
Identifiants
pubmed: 31533632
doi: 10.1186/s12864-019-6063-9
pii: 10.1186/s12864-019-6063-9
pmc: PMC6751898
doi:
Substances chimiques
Atf4 protein, mouse
0
Regulatory Factor X Transcription Factors
0
Rfx3 protein, mouse
0
SCRATCH2 protein, mouse
0
Transcription Factors
0
Activating Transcription Factor 4
145891-90-3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
718Subventions
Organisme : Genome Canada
ID : 174CDE
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