AGPAT1, a New Histone Acetyltransferase During Spermatogenesis.
Bibliographic record
Abstract
Male infertility is often associated with a relatively high DNA fragmentation level and an altered or incomplete chromatin packaging in mature spermatozoa. Spermatozoa acquire their unique chromatin packaging during the haploid phase of spermatogenesis, termed spermiogenesis. Hyperacetylation of histones H3 and H4 participates in this transition from a somatic histone organization to the compact protamined DNA found in spermatozoa. Because the control of histone acetylation is important for the genetic integrity of spermatids, we seek to identify new potential histone acetyltransferases (HATs) involved in this process using a functional assay. Since HATs bind covalently to their substrates, we hypothesize that new histone acetyltransferases may be identified by their interaction with hyperacetyled histones H4. We immunoprecitated hyperacetylated histone H4 from nuclear extracts from sonication resistant spermatids. To identify the molecular weight of co-immunoprecipitated HATs, we carried out in-gel HAT assays. Gel slices corresponding to a strong activity signal were cut out, and proteins identified by mass spectrometry. Cellular localization of the candidate was verified by immunofluorescence. The recombinant candidate protein was expressed and purified from E. coli JC201 cells and its in vitro histone acetyltransferase activity was assessed. A 70 kDa protein complex harboring an histone acetyltransferase activity was found associated with hyperacetylated histone H4. From mass spectrometry analysis of this band, we identified as a potential candidate AGPAT1 (1-acyl sn-glycerol-3-phosphate acyltransferase 1), an acyltransferase normally involved in phospholipids metabolism in somatic cells. Using immunofluorescence, AGPAT1 localized to the nucleus of elongating spermatids and the recombinant protein acetylated histones in vitro. Around 6 % of mammalian cell phospholipids is retained within the nuclear matrix providing substrate for lipid-mediated signaling events. Ten percent of nuclear phospholipids are associated with chromatin in somatic cells. The particular features conferring nuclear confinement of AGPAT1 in spermatids also remains to be elucidated but may be related to the relatively high lipids metabolism of the developing sperm head. That an acyltransferase may operate as an HAT during the chromatin remodeling is an original finding that may, for the first time, link lipid metabolism to the control of chromatin dynamics in the male gamete and could potentially be extended to somatic cells.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".