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| Status |
Public on Apr 24, 2013 |
| Title |
Endogenous mammalian histone H3.3 exhibits chromatin-related functions during development |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Background.
The histone variant H3.3 plays key roles in regulating chromatin states and transcription. However, the role of endogenous H3.3 in mammalian cells and during development has been less thoroughly investigated. To address this gap, we report the production and phenotypic analysis of mice and cells with targeted disruption of the H3.3-encoding gene, H3f3b.
Results.
H3f3b KO mice exhibit a semi-lethal phenotype traceable at least in part to defective cell division and chromosome segregation. H3f3b KO cells have widespread ectopic CENP-A protein localization suggesting one possible mechanism for defective chromosome segregation. KO cells have abnormal karyotypes and cell cycle profiles as well. The transcriptome and euchromatin-related epigenome were moderately affected by loss of H3f3b in MEFs with ontology most notably pointing to changes in chromatin regulatory and histone coding genes. Reduced numbers of H3f3b KO mice survive to maturity and almost all survivors from both sexes are infertile.
Conclusions.
Taken together, our studies suggest that endogenous mammalian histone H3.3 has important roles in regulating chromatin and chromosome functions that in turn are important for cell division, genome integrity, and development.
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| Overall design |
Examination of H3K9Ac and H3K4me3 in wild-type and H3.3 null MEFs
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| Contributor(s) |
O'Geen H, Bush KM, Yuen BT, Barrilleaux BL, Riggs JW, Cotterman R, Knoepfler PS |
| Citation(s) |
23570311 |
| Submission date |
Dec 19, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Henriette O'Geen |
| Organization name |
UC Davis
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| Street address |
1 Shields Avenue
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| City |
Davis |
| State/province |
CA |
| ZIP/Postal code |
95616 |
| Country |
USA |
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| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (8)
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| Relations |
| SRA |
SRP010408 |
| BioProject |
PRJNA151369 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE34546_RAW.tar |
824.2 Mb |
(http)(custom) |
TAR (of BED, GFF) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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