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Series GSE211941 Query DataSets for GSE211941
Status Public on Feb 09, 2024
Title CDCA7-associated global aberrant DNA hypomethylation translates to localized, tissue-specific transcriptional responses [ATAC-seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Disruption of Cell division cycle associated 7 (CDCA7) has been linked to aberrant DNA hypomethylation, but the impact of DNA methylation loss on transcription has not been investigated. Here, we show that CDCA7 is critical for maintaining global DNA methylation levels across multiple tissues in vivo. A pathogenic Cdca7 missense variant leads to the formation of large, aberrantly hypomethylated domains overlapping with the B genomic compartment but without affecting deposition of H3K9 trimethylation (H3K9me3). CDCA7-associated aberrant DNA hypomethylation translated to localized, tissue-specific transcriptional dysregulation that impacted large gene clusters. In brain, we identify CDCA7 as a transcriptional repressor and epigenetic regulator of clustered protocadherin isoform choice. Increased protocadherin isoform expression frequency is accompanied by DNA methylation loss, gain of H3K4 trimethylation (H3K4me3) and increased binding of the transcriptional regulator CCCTC-binding factor (CTCF). Overall, our in vivo work identifies a key role for CDCA7 in safeguarding tissue-specific expression of gene clusters via the DNA methylation pathway.
 
Overall design Assay for Transposase accessible chromatin combined with highthroughput sequencing (ATAC-seq) in P21 mouse Spleen
 
Contributor(s) Vukic M, Chouaref J, Della Chiara V, Dogan S, Ratner F, Hogenboom JZ, Epp T, Chawengsaksophak K, Vonk KK, Breukel C, Ariyurek Y, San Leon Granado D, Kloet SL, Daxinger L
Citation(s) 38335290
Submission date Aug 24, 2022
Last update date Feb 15, 2024
Contact name Lucia Daxinger
E-mail(s) L.Clemens-Daxinger@lumc.nl
Organization name Leiden Univeristy Medica Center
Street address Albinusdreef 2
City Leiden
ZIP/Postal code 2333ZA
Country Netherlands
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (2)
GSM6505953 Spleen, WT, ATAC
GSM6505954 Spleen, Cdca7G305V/G305V, ATAC
This SubSeries is part of SuperSeries:
GSE212007 CDCA7-associated global aberrant DNA hypomethylation translates to localized, tissue-specific transcriptional responses
Relations
BioProject PRJNA873029

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Supplementary file Size Download File type/resource
GSE211941_ATAC_P21_spleen.xlsx 585.6 Kb (ftp)(http) XLSX
GSE211941_RAW.tar 321.6 Mb (http)(custom) TAR (of BW)
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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