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Series GSE230341 Query DataSets for GSE230341
Status Public on Jan 14, 2024
Title KDM3A and KDM3B maintain naïve pluripotency through regulation of alternative splicing
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Histone modifying enzymes play a central role in maintaining cell identity by establishing a conducive chromatin environment for lineage specific transcription factor activity. Pluripotent embryonic stem cells (ESCs) identity is characterized by lower abundance of gene repression associated histone modifications that enables rapid response to differentiation cues. The KDM3 histone demethylase family remove the repressive histone H3 lysine 9 dimethylation (H3K9me2). Here we uncover a surprising role for the KDM3 proteins in the maintenance of the pluripotent state through post-transcriptional regulation. We find through immunoaffinity purification of the KDM3A or KDM3B interactome and proximity ligation assays that KDM3A and KDM3B interact with the RNA processing factors such as EFTUD2 and PRMT5. By generating double “degron” ESCs to degrade KDM3A and KDM3B in the rapid timescale of splicing, we find altered splicing independent of H3K9me2 status. These splicing changes partially resemble the splicing pattern of the more blastocyst like ground state of pluripotency and occurred in important chromatin and transcription factors such as Dnmt3b, Tbx3 and Tcf12. Our findings reveal non-canonical roles of histone modifying enzymes in splicing to regulate cell identity. Cells were plated, allowed to adhere overnight, then treated for four hours with dTAG-13.
Overall design Gene expression analysis of mouse ESCs (WT or KDM3A/KDM3B degron ESCs +/- dTAG-13 at four hours of degradation. Three biological replicates per condition.
Contributor(s) Dillingham C, Cormaty H, Morgan E, Tak A, Esgdaille D, Boutz P, Sridharan R
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Submission date Apr 22, 2023
Last update date Jan 15, 2024
Contact name Rupa Sridharan
Organization name University of Wisconsin
Department Wisconsin Institute for Discovery
Lab Sridharan
Street address 330 N. Orchard Street
City Madison
State/province WI
ZIP/Postal code 53715
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (9)
GSM7220187 E14_ESC_+dtag_4hrs_Rep1
GSM7220188 E14_ESC_+dtag_4hrs_Rep2
GSM7220189 E14_ESC_+dtag_4hrs_Rep3
BioProject PRJNA960637

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Supplementary file Size Download File type/resource
GSE230341_RAW.tar 3.5 Mb (http)(custom) TAR (of RESULTS)
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Raw data are available in SRA
Processed data provided as supplementary file

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