Changes in histone abundance and post-translational modifications in Rana [Lithobates] catesbeiana tissues during thyroid hormone-dependent metamorphosis
Bibliographic record
Abstract
Amphibian metamorphosis is thyroid hormone (TH)-dependent and involves extensive gene expression changes in differentiated tissues that result in organismal remodeling. This is likely to involve changes in the epigenome that are poorly understood. We used tandem mass spectrometry (MS/MS) to investigate global variations in histone abundance and histone post-translational modifications (PTMs) during natural metamorphosis to identify putative epigenomic mediators of TH-mediated postembryonic development. Blood, liver, and tailfin from five Rana (Lithobates) catesbeiana (American bullfrog) individuals were collected from functionally athyroid premetamorphic tadpoles and from tadpoles at metamorphic climax (maximal TH levels). Only blood and liver were collected from five individual R. catesbeiana frogs (suprabasal TH levels), as the tailfin is resorbed by this stage. Nuclei were acid extracted to enrich for basic proteins, including histones and other chromatin-associated proteins. MS/MS data were queried against the R. catesbeiana proteome using open search parameters to capture modified histone peptides and stringent statistical evaluation was performed. The abundance of multiple histone variants and isoforms changed throughout metamorphosis. In particular, histone H1.0 increased over the metamorphic stages in all three tissue with a concurrent decrease in H1.3 in blood and liver. Further, H2A variants H2A.X and macroH2A.1 decreased over metamorphosis in blood while H2A type 2-C, H2A.Z-2 and macroH2A.2 increased in liver. We identified putative changes in histone PTMs by analyzing the abundance of peptides carrying mass shifts corresponding to methylation, acetylation and phosphorylation. Our findings include an increase in H1.3 mono- and dimethylation in blood and liver over metamorphosis and suggest a temporary increase of H3.2 phosphorylation at metamorphic climax in liver. To our knowledge, this is the first non-targeted analysis of histone isoform and variant abundance and PTMs during TH-mediated amphibian metamorphosis. Due to the conserved nature of TH signaling, our findings broaden our understanding of the coordinated variations in histone abundance and PTMs that occur across all histone families to direct the tissue-specific transitions that are critical for TH-driven development in amphibians and other vertebrate species.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".