|
Status |
Public on Feb 15, 2019 |
Title |
UTX and 53BP1 co-regulate genetic programs for neural differentiation of human embryonic stem cells [RNA-seq] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
UTX is a histone H3 lysine 27 demethylase required for development. However, the mechanisms underlying developmental gene regulation by UTX are unclear. Here, we discovered a molecular interaction between UTX and 53BP1 that regulates gene expression in a human neurogenesis model. Human 53BP1 contains a UTX-binding site that diverges from its mouse homolog by 41%, and our data suggest that the UTX-53BP1 interaction is conserved in primates but not rodents. ChIP-Seq revealed that the genome-wide targets of UTX and 53BP1 overlap by 84%. We used CRISPR-Cas9 to generate mutations of 53BP1 and UTX in human embryonic stem cells, and found that both 53BP1 and UTX are required to promote the expression of hundreds of neurogenic genes during neural differentiation. Further, 53BP1 is required for human neural progenitor differentiation into neurons. Our findings suggest that the UTX-53BP1 interaction controls gene expression important for neural differentiation in humans.
|
|
|
Overall design |
Examination of 2 transcription factors as 53BP1 and UTX binding sites in hESC and hNPC, H3K27me3 and H3K27ac in WT and 53BP1 KO cells. Intergrated analysis with transcriptome.
|
|
|
Citation(s) |
30718900 |
Submission date |
Dec 14, 2017 |
Last update date |
Mar 27, 2019 |
Contact name |
Beisi Xu |
E-mail(s) |
beisi.xu@stjude.org
|
Organization name |
St Jude Children's Research Hosipital
|
Department |
Center for Applied Bioinformatics
|
Street address |
262 Danny Thomas Pl
|
City |
Memphis |
State/province |
Tennessee |
ZIP/Postal code |
38105 |
Country |
USA |
|
|
Platforms (3) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
Samples (27)
|
|
This SubSeries is part of SuperSeries: |
GSE108116 |
UTX and 53BP1 co-regulate genetic programs for neural differentiation of human embryonic stem cells |
|
Relations |
BioProject |
PRJNA422469 |
SRA |
SRP126791 |