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| Status |
Public on May 09, 2023 |
| Title |
Sperm chromatin structure and reproductive fitness are altered by substitution of a single amino acid in mouse Protamine 1 [scRNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Conventional dogma presumes that protamine-mediated DNA compaction in sperm is achieved by electrostatic interactions between DNA and the arginine-rich core of protamines. However, phylogenetic analysis reveals several non-arginine residues conserved within, but not across species. The significance of these residues or post-translational modifications are poorly understood. Here, we investigated the functional role of K49, a rodent-specific lysine residue in mouse protamine 1 (P1) that is acetylated early in spermiogenesis and retained in sperm. In vivo, alanine substitution (P1 K49A) results in loss of programmatic histone retention, decreased sperm motility, decreased male fertility, and in zygotes, premature P1 removal from paternal chromatin, altered DNA replication, and embryonic arrest. In vitro, P1 K49A decreases protamine-DNA binding and alters DNA compaction/decompaction kinetics. Hence, a single amino acid substitution outside the P1 arginine core is sufficient to profoundly alter protein function and developmental outcomes, suggesting that protamine non-arginine residues are essential for reproductive fitness.
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| Overall design |
Two-cell embryos were collected from mice between 26 and 28 hours post fertilization and each embryo was immediately placed into a single well of a plexWell Rapid Single Cell plate, which was then frozen until sequencing.
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| Web link |
https://www.nature.com/articles/s41594-023-01033-4
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| |
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| Contributor(s) |
Hammoud SS, Li JZ |
| Citation(s) |
37460896 |
| |
| Submission date |
Feb 14, 2023 |
| Last update date |
Aug 08, 2023 |
| Contact name |
Qianyi Ma |
| E-mail(s) |
qzm100@gmail.com
|
| Organization name |
University of Michigan
|
| Department |
Human Genetics
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| Street address |
1141 E Catherine St
|
| City |
Ann Arbor |
| State/province |
MI |
| ZIP/Postal code |
48109 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (48)
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| This SubSeries is part of SuperSeries: |
| GSE225271 |
Sperm chromatin structure and reproductive fitness are altered by substitution of a single amino acid in mouse Protamine 1 |
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| Relations |
| BioProject |
PRJNA934867 |
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