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Series GSE66436 Query DataSets for GSE66436
Status Public on Feb 01, 2021
Title ST18 represents a novel transcriptional repressor ensuring proper expression kinetics during early cortical development
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Cortical development is a tightly spatiotemporally regulated process in which cell-fate specification is accompanied by stable resetting of transcriptional programs. However, the full repertoire of transcriptional regulators orchestrating such transcriptome changes remains largely incomprehensive. Applying a bioinformatics predictive approach we aimed to identify novel transcription factors contriuting to transcriptional reprogramming during embryonic neurogenesis and identified the neuronal tissue specific transcription factor St18 to be essential for neurogenesis in vitro and in vivo. We find that embryonic stem cells deficient for St18 are not able to efficiently differentiate along neuronal lineage and St18 depleted cells in the developing cortex do not elongate in shape and reside in the VZ/SVZ region but display premature expression of the upper layer neuronal marker Satb2. Relation of St18 binding to genes deregulated upon St18 depletion in vivo revealed St18 to function as transcriptional repressor at the time when neurogenesis is initiated. St18 ensures efficient onset of cortical neurogenesis by inhibiting expression of the self-renewal maintaining factor Hes1 that represses differentiation genes in neuronal progenitors as well as downregulation of genes that are essential for differentiation into mesodermal and endodermal lineage such as Lama5, Traf4 and Tab1. Furthermore we find this transcriptional repressor to be bound to genes that are important for later stages of neurogenesis when the neuronal circuitry is established likely to keep them in repressed state in the time window of neurogenesis when they are not yet required. These genes important for axon guidance and neurite outgrowth are subsequently prematurely upregulated in St18 depleted cortical cells. We further observe St18 to be bound to a significant fraction of intergenic enhancers where it regulates expression of nearest genes that Our data establish St18 as a novel transcriptional regulator during early onset of cortical neurogenesis that is essential to ensure timely expression kinetics of phase and lineage specific genes.
Overall design 4 replicates of NTC electroporated brains and 4 replicates of shSt18 electroporated brains have been analyzed
Contributor(s) Garding A, Jung J, Pataskar A, Thakurela S, Tiwari V
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Submission date Mar 02, 2015
Last update date Feb 01, 2021
Contact name Abhijeet Pataskar
Organization name Institute of Molecular Biology
Street address Ackermannweg 4
City Mainz
ZIP/Postal code 55128
Country Germany
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (11)
GSM1622412 ST18_early_rep1
GSM1622413 ST18_early_rep2
GSM1622414 ST18_early_rep3
BioProject PRJNA276909
SRA SRP055720

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE66436_EdgeR_St18.xls.gz 822.8 Kb (ftp)(http) XLS
GSE66436_NormalizedEnrichment_Promoter_st18.txt.gz 199.5 Kb (ftp)(http) TXT
GSE66436_NormalizedTagCounts.xlsx 2.1 Mb (ftp)(http) XLSX
GSE66436_Peaks_enrichment.xls.gz 202.6 Kb (ftp)(http) XLS
GSE66436_ST18.wig.gz 12.8 Mb (ftp)(http) WIG
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Raw data are available in SRA
Processed data are available on Series record

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