SURVIVIN IN SYNERGY WITH BAF/SWI COMPLEX BINDS BIVALENT CHROMATIN REGIONS AND ACTIVATES DNA DAMAGE RESPONSE IN CD4+ T CELLS
Bibliographic record
Abstract
Abstract This study explores a regulatory role of oncoprotein survivin on the bivalent regions of chromatin (BvCR) characterized by concomitant deposition of trimethylated lysine of histone H3 at position 4 (H3K4me3) and 27 (H3K27me3). Intersect between BvCR and chromatin sequences bound to survivin demonstrated their co-localization on cis -regulatory elements of genes which execute DNA damage control in primary human CD4 + cells. Survivin anchored BRG1-complex to BvCR to repress DNA damage repair genes in IFNγ-stimulated CD4 + cells. In contrast, survivin inhibition shifted the functional balance of BvCR in favor of H3K4me3, which activated DNA damage recognition and repair. Co-expression of BRG1, survivin and IFNγ in CD4 + cells of patients with rheumatoid arthritis identified arthritogenic BRG1 hi cells abundant in autoimmune synovia. Immunomodulating drugs inhibited the subunits anchoring BRG1-complex to BvCR, which changed the arthritogenic profile. Together, this study demonstrates the function of BvCR in DNA damage control of CD4 + cells offering an epigenetic platform for survivin and BRG1-complex targeting interventions to combat autoimmunity. Summary This study shows that bivalent chromatin regions accommodate survivin which represses DNA repair enzymes in IFNγ-stimulated CD4 + T cells. Survivin anchors BAF/SWI complex to these regions and supports autoimmune profile of T cells, providing novel targets for therapeutic intervention.
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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) | 0.002 | 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".