 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Feb 09, 2024 |
| Title |
CDCA7-associated global aberranDNA hypomethylation translates to localized, tissue-specific transcriptional responses [WGBS] |
| Organism |
Mus musculus |
| Experiment type |
Methylation 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 |
Whole Genome Bisulfite sequencing (WGBS) in mouse P21 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 25, 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) |
|
| Samples (4)
|
|
| This SubSeries is part of SuperSeries: |
| GSE212007 |
CDCA7-associated global aberrant DNA hypomethylation translates to localized, tissue-specific transcriptional responses |
|
| Relations |
| BioProject |
PRJNA873269 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE212005_RAW.tar |
694.8 Mb |
(http)(custom) |
TAR (of BW) |
| GSE212005_hyperDMLs.bed.gz |
25.1 Kb |
(ftp)(http) |
BED |
| GSE212005_hypoDMLs.bed.gz |
38.2 Mb |
(ftp)(http) |
BED |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...