Identification and characterization of TGFβ-dependent and -independent cis-regulatory modules in the C4ST-1/CHST11 locus
Bibliographic record
Abstract
Chondroitin-4-sulfotransferase-1(C4ST-1)/carbohydrate sulfotransferase 11 (CHST11) is a Golgi-bound enzyme involved in the biosynthesis of the glycosaminoglycan chondroitin sulfate. The sulfation pattern of chondroitin is tightly regulated during development, injury and disease, with the temporal and spatial expression of chondroitin sulfotransferase genes believed to be a crucial determinant of the fine balance of chondroitin sulfation. We have previously identified mouse C4st-1 as a target gene of ligands of the TGFbeta superfamily of growth factors, which could positively regulate C4st-1 expression in a number of cell types. We have also shown that a gene trap loss-of-function mutation in C4st-1 leads to severe skeletal abnormalities during mouse embryogenesis. In addition, we described a highly specific temporal and spatial expression pattern of C4st-1 during mouse embryogenesis. However, the transcriptional regulatory mechanisms that control C4st-1 gene expression remain unexplored. In order to gain knowledge on the transcriptional regulation of C4ST-1, we used a bioinformatical approach to identify conserved putative long-range cis-regulatory modules in a region of 120 kb spanning the 5' end of the C4ST-1 gene. Luciferase reporter assays in human HEK293T and mouse NmuMG cells identified a functional C4ST-1 promoter, as well as a number of cis-regulatory modules able to positively and negatively regulate C4ST-1 expression. Moreover, we identified TGFbeta- responsive regulatory modules that can function in a cell type-specific fashion. Taken together, our results identify TGFbeta-dependent and -independent cis-regulatory modules of the C4ST-1 gene.
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 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.001 | 0.001 |
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".