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Series GSE130384 Query DataSets for GSE130384
Status Public on Nov 29, 2019
Title Cdk5-mediated phosphorylation ensures robust neuronal differentiation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary Tet3 converts 5-methylcyotsine to 5-hydroxymethylcytosine (5hmC), although it remains unclear how its functions can be regulated. We showed that Tet3 is phosphorylated by cyclin-dependent kinase 5 at a highly conserved serine residue within its catalytic domain, which leads to an increase in its dioxygenase activity in vitro. Interestingly, when stably expressed in Tet triple-knockout mouse embryonic stem cells (mESCs), wild-type Tet3 elicited higher 5hmC enrichment and expression of genes involved in neurogenesis whereas phosphor-mutant Tet3 caused elevated 5hmC and expression of metabolic pathways genes. Expression of wild-type, but not phosphor-mutant Tet3 in Tet3-knockout mESCs, causes optimal expression of BRN2, Hes1 and Hey2 transcription factors which lead to robust terminal differentiation measured by MAP2 expression. Taken together, our results suggest that cdk5-mediated phosphorylation of Tet3 ensures robust activation of neuronal transcriptional programs during differentiation.
 
Overall design RNA-seq, ChIP-seq (H3K27ac) and 5hmC-DNA-IP in Tet1,2,3 triple knockout mouse embryonic stem cells rescued with wild-type or phosphor-mutant Tet3
 
Contributor(s) Ong CT, Swarnaseetha A, Tham GH, Rao VK, Lin WQ
Citation(s) 31807777
BioProject PRJNA517055
Submission date Apr 26, 2019
Last update date Mar 02, 2020
Contact name Swarnaseetha Adusumalli
E-mail(s) swarna@tll.org.sg
Organization name Temasek Life Sciences Laboratory
Street address 1 Research Link, National University of Singapore
City Singapore
ZIP/Postal code 117604
Country Singapore
 
Platforms (1)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (24)
GSM3737217 AA10_K27ac_Rep1
GSM3737218 AA10_K27ac_Rep2
GSM3737219 AA10_MNase_Rep1
Relations
SRA SRP182030

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

Supplementary file Size Download File type/resource
GSE130384_AAhighWT_Dhmr_sites.bed.gz 72.8 Kb (ftp)(http) BED
GSE130384_DEG.xlsx 1.2 Mb (ftp)(http) XLSX
GSE130384_RAW.tar 3.0 Gb (http)(custom) TAR (of BW)
GSE130384_WThighAA_Dhmr_sites.bed.gz 101.3 Kb (ftp)(http) BED
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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