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| Status |
Public on Mar 06, 2015 |
| Title |
BRD4 dynamics reveal novel acrosome-dependent chromatin reorganization during post-meiotic mammalian sperm development |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
During the post-meiotic phase of spermatogenesis, transcription is progressively repressed as the nuclei of haploid spermatids are compacted through a dramatic chromatin reorganization involving hyper-acetylation and replacement of most histones with sperm-specific protamines. Although BRDT has been shown to function in transcription as well as histone removal in post-meiotic spermatids, it is unknown whether other BET family proteins play a role. Immunofluorescence of mouse testes revealed BRD4 in a complete ring around the nuclei of spermatids containing hyper-acetylated histones. The BRD4 ring lies directly adjacent to the acroplaxome, or the cytoskeletal base of the acrosome, and does not form in acrosomal mutant mice. ChIP sequencing in round spermatids revealed enrichment of BRD4 and acetylated histone H3 and H4 at the promoters of active genes. GO Term analysis showed that BRD4 and BRDT bind to distinct subsets of spermatogenesis-specific genes. Association of BRD4 with Cyclin T1 decreases as spermatogenesis progresses despite a persistence of association with acetylated H4. Moreover, acetylated histones are removed from the condensing spermatid nucleus in a wave following the progressing acrosome. These data provide evidence for an interesting mechanism in which BRD4 and perhaps acetylated histones are removed from the spermatid genome via the progressing acrosome as transcription is repressed.
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| Overall design |
Single replicates each of Brd4, H3K9me3, H3K9ac, H4K5ac, H4K8ac, H4K12ac, H4K16ac, H4Kac (pan-acetyl antibody), and input in mouse round spermatid cells; input is used to control for local sonication efficiency bias.
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| Contributor(s) |
Bryant JM, Donahue G, Wang X, Meyer-Ficca M, Otte GL, Luense LJ, Bartolomei MS, Blobel GA, Meyer RG, Garcia BA, Berger SL |
| Citation(s) |
25691659 |
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| Submission date |
Apr 04, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Gregory Donahue |
| Organization name |
The University of Pennsylvania
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| Department |
Cell & Developmental Biology
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| Lab |
Zaret Lab
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| Street address |
3400 Civic Center Blvd, Bldg 421
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA243627 |
| SRA |
SRP040980 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE56526_RAW.tar |
5.2 Gb |
(http)(custom) |
TAR (of BED, BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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