Exploring the Roles of Nuclear Deubiquitinating Enzymes BAP1 and MYSM1 in Hematopoiesis and Immune Cell Functions
Bibliographic record
Abstract
Ab -antibody ADCC -antibody-dependent cellular cytotoxicity AGM -aorta-gonad-mesonephros AID -activation-induced cytidine deaminase APC -antigen presenting cell(s) BAP1 -BRCA1-associated protein 1 BARD1 -BRCA1-associated RING domain protein 1 BCR -B-cell receptor BER -base excision repair BM -bone marrow BRCA1 -breast cancer type 1 susceptibility protein cDC -conventional dendritic cell CDP -conventional dendritic cell progenitors CLP -common lymphoid progenitor CMP -common myeloid progenitor CSR -class-switch recombination DC -dendritic cell DH -diversity gene segment of the immunoglobulin heavy chain DNMT -DNA methyltransferase DSB -double-strand break DZ -dark zone E2A -E2A transcription factor EBF1 -early B-cell factor 1 ECM -extracellular matrix ETS -E26 transformation-specific FDC -follicular dendritic cell FO B -follicular B cell FOXK1/2 -forkhead box kinase 1 and 2 GC -germinal center GMP -granulocyte/macrophage progenitor H2AK119ub -mono-ubiquitination at lysine 119 of histone H2A H3K4me3 -tri-methylation at lysine 4 of histone H3 H3K27me3 -tri-methylation at lysine 27 of histone H3 H3S10p -phosphorylation at serine 10 of histone H3 H3K14ac -acetylation at lysine 14 of histone H3 HAT -histone acetyl transferases HDR -homology-directed repair HSC -hematopoietic stem cell HSPC -hematopoietic stem and progenitor cell ICOS -inducible T-cell co-stimulator Ig -immunoglobulin IgC -immunoglobulin constant domain IgV -immunoglobulin variable domain IFN -interferon IL -interleukin ILC -innate lymphoid cell INO80 -INO80 chromatin remodeling complex IP3R3 -inositol 1,4,5-trisphosphate receptor, type 3 IRF -interferon regulatory factor JL/JH -joining gene segment of the immunoglobulin light/heavy chain KDM1B -lysine-specific histone demethylase KLF5 -Kruppel-like factor 5 LT-HSC -long-term hematopoietic stem cell LMPP -lymphoid-primed multipotent progenitor LZ -light zone MEP -megakaryocyte erythroid progenitor MHC -major histocompatibility complex MMR -mismatch repair MPP -multipotent progenitor cell MSH2/6 -MSH2/6 mismatch repair complex MYSM1 -Myb-like SWIRM and MPN domains 1 MZ B -marginal zone B cells NHEJ -nonhomologous end joining NK cell -natural killer cell OGT -O-linked β-N-acetylglucosamine (O-GlcNAc) transferase PAMP -pathogen-associated molecular pattern PAX5 -paired box protein 5 PC -plasma cell PCGF -Polycomb group ring finger subunit PD1 -programmed cell death protein 1 pDC -plasmacytoid dendritic cell PGC1α -peroxisome proliferator-activated receptor-γ coactivator 1-α Pol -polymerase PRC -polycomb repressive complex RAD51 -RAD51 recombinase Rag -recombination activation gene RUNX1 -runt-related transcription factor 1 Abstract Hematopoiesis, the process by which the full repertoire of blood cells is established from the hematopoietic stem cells (HSCs), depends on a well-coordinated regulatory network of gene expression.BAP1 and MYSM1 are both deubiquitinases (DUBs) that can regulate gene expression and other cellular processes, through their direct catalytic activity on the repressive epigenetic mark histone H2AK119ub, as well as on several other substrates.In previous research, mutations of Bap1 and Mysm1 have been associated with defects in hematopoiesis in both mouse and human, yet our knowledge of the mechanistic role of these two DUBs in the development and the function of blood and immune cells remains limited.In the current study, we aim to explore the potential regulatory role of BAP1 and MYSM1 in hematopoietic cell development and immune response.We characterize a cell intrinsic role of BAP1 in B lymphocyte development and in antibody mediated immune response.We demonstrates its central role in the regulation of the genome-wide landscapes of histone H2AK119ub and downstream transcriptional programs of cell cycle progression, DNA damage response, and many other biological processes involved in B cell development, B cell activation, and humoral immunity.We also report a profound similarity in the developmental, hematopoietic, and immune phenotypes resulting from the loss of MYSM1 catalytic function and the full loss of MYSM1 protein, confirming that MYSM1 acts via its DUB catalytic activity specifically in early hematopoietic progenitors to allow normal development of hematopoietic cells, including lymphocytes and dendritic cells (DCs).Overall, our work expands the knowledge of the critical roles of BAP1 and MYSM1 in vivo in hematopoiesis, leukocyte development, immune responses, and other aspects of mammalian physiology.
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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 | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".