A267 EPIGENETIC ERASERS HDAC1 AND HDAC2 DRIVE INTESTINAL EPITHELIAL CELL BEHAVIOR
Bibliographic record
Abstract
Histone deacetylase Hdac1 and Hdac2 regulate gene expression and protein function by removing acetyl groups on lysines. Hdac1 and Hdac2 influence many biological processes, from chromatin organization and cell differentiation, to cell cycle and inflammation. As we reported before, intestinal epithelial cell (IEC) Hdac1 and Hdac2 are essential regulators of intestinal homeostasis related to differentiation and inflammatory responses, among others. However, the specific Hdac1 and Hdac2 downstream targets still remain to be determined. To better understand the molecular mechanisms driven by Hdac1 and Hdac2 in IEC, we need a full picture of the proteomic IEC-specific changes occurring upon Hdac1 and/or Hdac2 deletion or HDAC pharmacological inhibition. Floxed mice for both Hdac1 and Hdac2 alleles were crossed with villin-Cre mice, to insure IEC-specific deletion. 3-month-old mutated mice were used for the experiments. For pharmacological inhibition, the HDAC class I inhibitor CI994 was injected intraperitoneally in 2-month-old Balb/c mice, once a day for 5 days. Jejunal epithelial cells were isolated by the EDTA method. Cell lysates from control IEC, from Hdac1, Hdac2 and Hdac1/2 deleted IEC and from CI994 treated IEC were labeled with different isobaric chemical tags (Tandem Mass Tag reagents). Labeled cell lysates were mixed, digested with trypsin and used for liquid chromatography-tandem mass spectrometry and data analysis. Bioinformatic pathway analysis was achieved with the DAVID 2.0 software for gene ontology biological processes, for proteins showing two-fold increases or decreases. More than 3000 proteins were detected by mass spectrometry analysis for each sample. Differential protein expression was observed in Hdac1/2- (800), Hdac1- (150) or Hdac2-depleted (200), and CI994-treated IEC (150). Translation and chromatin assembly were among the top biological processes respectively up- and down-regulated in Hdac1/2-depleted IEC, with decreased expression of goblet and Paneth cell proteins (Zg16, Muc2, Lyz1) and increased enterocyte proteins (Sis, Alpi). Interestingly, while the top negative biological process for both Hdac1- and Hdac2-depleted IEC was “antigen processing and presentation of peptide antigen”, the immune response pathway and the protein kinase/intracellular signaling cascade pathway were increased respectively in Hdac1 and Hdac2 knockout IEC. Surprisingly, CI994-treated IEC displayed “homeostatic process”, as the top increased biological process, and chromatin assembly, as the top decreased biological process. Targeting HDAC, genetically or pharmacologically, changes IEC behavior. Hdac1 and Hdac2 regulate similar as well as distinct protein expression programs, thereby indicating specific molecular functions in IEC. CCC, CIHR
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".