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Series GSE76129 Query DataSets for GSE76129
Status Public on Dec 21, 2019
Title ZNF599 and DNMT3A coordinately control nuclear envelope organization by repression of SUN4 expression
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Human-specific KRAB-ZF proteins are putative transcription factors and correlate with human cognitive and linguistic ability. The typical KRAB-ZF protein ZNF599 has been implicated in developmental delay. However, the underlying molecular mechanism is elusive. Here, we show a specific interaction of ZNF599 with DNMT3A, but not DNMT3B or DNMT1. Using CRISPR/Cas9, we generated a ZNF599-/- cell line that shows an irregular nuclear morphology with blebbings, dents and ridges. Interestingly, the irregular nuclear shape can be rescued by complement expression of wt ZNF599, but not with ZNF599 L178F, a mutant that has been described in patients with mental retardation. With transcriptome analysis by next-generation sequencing, we found several genes misregulated in ZNF599-/- cells, particularly an upregulation of SUN4, also known as SPAG4. Consistently, ectopic expression of GFP-SUN4 in wt cells shows a similar effect on nuclear morphology as observed in ZNF599-/- cells. Besides ZNF599, DNMT3A dependent DNA methylation is also required for repression of Sun4 expression as we observe an upregulation of Sun4 in murine Dnmt3a-/- cells. Thus, we conclude that ZNF599 and DNMT3A coordinately control SUN4 expression to regulate nuclear envelope organization providing a potential insight into the molecular mechanism of development delay pathology.
 
Overall design HELA cells with wt genotype or ZNF599 -/- genotype were analysed in 4 independent replicates
 
Contributor(s) Smets M, Qin W
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Submission date Dec 17, 2015
Last update date Dec 22, 2019
Contact name Martha Smets
E-mail(s) smets@bio.lmu.de
Organization name Ludwig-Maximilians University Munich
Department Department Biology II
Street address GroƟhaderner Str. 2
City Martinsried
ZIP/Postal code 82152
Country Germany
 
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (8)
GSM1974835 ZNF599_KO1
GSM1974836 ZNF599_KO2
GSM1974837 ZNF599_KO3
Relations
BioProject PRJNA306375
SRA SRP067531

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
GSE76129_RAW.tar 1.5 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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