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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 12, 2015 |
| Title |
Hira is essential for normal transcriptional regulation and efficient de novo DNA methylation during mouse oogenesis |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
The integrity of chromatin, which provides a dynamic template for all DNA related processes in eukaryotes, is maintained through replication dependent and independent assembly pathways. To address the role of replication independent histone deposition, we deleted the histone H3.3 chaperone Hira in developing mouse oocytes. We show that chromatin of non-replicative developing oocytes is highly dynamic, and that lack of continuous H3.3/H4 deposition alters chromatin structure, resulting in increased DNase I sensitivity, the accumulation of DNA damage, and, ultimately, a severe fertility phenotype. On the molecular level, abnormal chromatin structure leads to a dramatic decrease in the dynamic range of gene expression, the appearance of spurious transcripts, and inefficient de novo DNA methylation. In contrast to the only minor transcriptional phenotype observed in mouse pluripotent cells, we unequivocally show the importance of histone replacement and chromatin homeostasis for transcriptional regulation and normal developmental progression in an in vivo context.
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| Overall design |
DNA methylome using BS-Seq of Hira wild-type and Hira deleted MII oocytes
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| Contributor(s) |
Nashun B, Hill PW, Smallwood SA, Dharmalingam G, Amouroux R, Clark SJ, Sharma V, Ndjetehe E, Pelczar P, Festenstein R, Kelsey G, Hajkova P |
| Citation(s) |
26549683 |
| Submission date |
Mar 06, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Gavin Kelsey |
| Organization name |
The Babraham Institute
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| Street address |
Babraham Research Campus
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| City |
Cambridge |
| ZIP/Postal code |
CB22 3AT |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (28)
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| Relations |
| BioProject |
PRJNA277485 |
| SRA |
SRP055927 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE66629_RAW.tar |
675.3 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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