ArticleProceedings of the National Academy of Sciences of the United States of America2016
The histone H2A deubiquitinase Usp16 regulates hematopoiesis and hematopoietic stem cell function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 117 citations in OpenAlex.
- Mechanisms of Hematopoietic Stem Cell Aging and Emerging Rejuvenation Strategies.Stem cell reviews and reports · 2026Review
- ZnF-UBP domains regulate deubiquitinase activity by relieving ubiquitin product inhibition.Nature communications · 2026Article
- USP16 drives psoriasis progression by deubiquitinating and stabilizing NLRP3 in keratinocytes.JCI insight · 2026Article
- Epigenetic dysregulation of B‑cells in autoimmune diseases and lymphomas (Review).International journal of molecular medicine · 2026Review
- Mono-ubiquitination of histone H2A lysine 119 (H2AK119Ub): its multifaceted role in biology and implication in diseases.MedScience · 2026Review
- EnP1 exploits H2Aub-dependent epigenetic reprogramming to promote microsporidia proliferation in host cells.PLoS pathogens · 2026Article
- USP16 S-nitrosylation aggravates coronary microembolization-induced myocardial injury via repressing KDM1A-mediated glutathione homeostasis.Nature communications · 2025Article
- MYSM1 promotes lung adenocarcinoma progression via TRAF2/3-mediated activation of MAPK and non-canonical NF-κB pathways.NPJ precision oncology · 2025Article
- Usp7 Regulates Glial Lineage Cell-Specific Transcription Factors by Modulating Histone H2B Monoubiquitination.International journal of stem cells · 2024Article
- Structural and mechanistic basis for nucleosomal H2AK119 deubiquitination by single-subunit deubiquitinase USP16.Nature structural & molecular biology · 2024Article
- B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1.Frontiers in immunology · 2024Article
- FGF18 alleviates hepatic ischemia-reperfusion injury via the USP16-mediated KEAP1/Nrf2 signaling pathway in male mice.Nature communications · 2023Article
- The transcriptome of HTLV-1-infected primary cells following reactivation reveals changes to host gene expression central to the proviral life cycle.PLoS pathogens · 2023Article
- Genetic dissection of triplicated chromosome 21 orthologs yields varying skeletal traits in Down syndrome model mice.Disease models & mechanisms · 2023Article
- Review
- Critical role of lncEPAT in coupling dysregulated EGFR pathway and histone H2A deubiquitination during glioblastoma tumorigenesis.Science advances · 2022Article
- USP16-mediated histone H2A lysine-119 deubiquitination during oocyte maturation is a prerequisite for zygotic genome activation.Nucleic acids research · 2022Article
- Srebf1c preserves hematopoietic stem cell function and survival as a switch of mitochondrial metabolism.Stem cell reports · 2022Article
- Review
- MYSM1 inhibits human colorectal cancer tumorigenesis by activating miR-200 family members/CDH1 and blocking PI3K/AKT signaling.Journal of experimental & clinical cancer research : CR · 2021Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Epigenetic mechanisms play important regulatory roles in hematopoiesis and hematopoietic stem cell (HSC) function. Subunits of polycomb repressive complex 1 (PRC1), the major histone H2A ubiquitin ligase, are critical for both normal and pathological hematopoiesis; however, it is unclear which of the several counteracting H2A deubiquitinases functions along with PRC1 to control H2A ubiquitination (ubH2A) level and regulates hematopoiesis in vivo. Here we investigated the function of Usp16 in mouse hematopoiesis. Conditional deletion of Usp16 in bone marrow resulted in a significant increase of global ubH2A level and lethality. Usp16 deletion did not change HSC number but was associated with a dramatic reduction of mature and progenitor cell populations, revealing a role in governing HSC lineage commitment. ChIP- and RNA-sequencing studies in HSC and progenitor cells revealed that Usp16 bound to many important hematopoietic regulators and that Usp16 deletion altered the expression of genes in transcription/chromosome organization, immune response, hematopoietic/lymphoid organ development, and myeloid/leukocyte differentiation. The altered gene expression was partly rescued by knockdown of PRC1 subunits, suggesting that Usp16 and PRC1 counterbalance each other to regulate cellular ubH2A level and gene expression in the hematopoietic system. We further discovered that knocking down Cdkn1a (p21cip1), a Usp16 target and regulated gene, rescued the altered cell cycle profile and differentiation defect of Usp16-deleted HSCs. Collectively, these studies identified Usp16 as one of the histone H2A deubiquitinases, which coordinates with the H2A ubiquitin ligase PRC1 to regulate hematopoiesis, and revealed cell cycle regulation by Usp16 as key for HSC differentiation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.