دورية أكاديمية
أعرض في EDS

ASXLs binding to the PHD2/3 fingers of MLL4 provides a mechanism for the recruitment of BAP1 to active enhancers.

التفاصيل البيبلوغرافية
العنوان: ASXLs binding to the PHD2/3 fingers of MLL4 provides a mechanism for the recruitment of BAP1 to active enhancers.
المؤلفون: Zhang Y; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.; Department of Biochemistry, Case Western Reserve University, Cleveland, OH, 44106, USA., Xie G; Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, 20892, USA., Lee JE; Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, 20892, USA., Zandian M; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, 80045, USA., Sudarshan D; St-Patrick Research Group in Basic Oncology, Oncology Division of CHU de Québec-Université Laval Research, Laval University Cancer Research Center, Quebec City, QC, G1R 3S3, Canada., Estavoyer B; Maisonneuve-Rosemont Hospital Research Center, Montréal, QC, H1T 2M4, Canada., Benz C; Department of Chemistry, BMC, Uppsala University, Uppsala, 75237, Sweden., Viita T; St-Patrick Research Group in Basic Oncology, Oncology Division of CHU de Québec-Université Laval Research, Laval University Cancer Research Center, Quebec City, QC, G1R 3S3, Canada., Asgaritarghi G; St-Patrick Research Group in Basic Oncology, Oncology Division of CHU de Québec-Université Laval Research, Laval University Cancer Research Center, Quebec City, QC, G1R 3S3, Canada., Lachance C; St-Patrick Research Group in Basic Oncology, Oncology Division of CHU de Québec-Université Laval Research, Laval University Cancer Research Center, Quebec City, QC, G1R 3S3, Canada., Messmer C; Maisonneuve-Rosemont Hospital Research Center, Montréal, QC, H1T 2M4, Canada., Simonetti L; Department of Chemistry, BMC, Uppsala University, Uppsala, 75237, Sweden., Sinha VK; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, 80045, USA., Lambert JP; St-Patrick Research Group in Basic Oncology, Oncology Division of CHU de Québec-Université Laval Research, Laval University Cancer Research Center, Quebec City, QC, G1R 3S3, Canada., Chen YW; Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan, ROC., Wang SP; Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan, ROC., Ivarsson Y; Department of Chemistry, BMC, Uppsala University, Uppsala, 75237, Sweden., Affar EB; Maisonneuve-Rosemont Hospital Research Center, Montréal, QC, H1T 2M4, Canada.; Department of Medicine, University of Montréal, Montréal, QC, H3C 3J7, Canada., Côté J; St-Patrick Research Group in Basic Oncology, Oncology Division of CHU de Québec-Université Laval Research, Laval University Cancer Research Center, Quebec City, QC, G1R 3S3, Canada. jacques.cote@crchudequebec.ulaval.ca., Ge K; Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, 20892, USA. kai.ge@nih.gov., Kutateladze TG; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, 80045, USA. tatiana.kutateladze@cuanschutz.edu.
المصدر: Nature communications [Nat Commun] 2024 Jun 07; Vol. 15 (1), pp. 4883. Date of Electronic Publication: 2024 Jun 07.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Tumor Suppressor Proteins*/metabolism , Tumor Suppressor Proteins*/genetics , Histone-Lysine N-Methyltransferase*/metabolism , Histone-Lysine N-Methyltransferase*/genetics , Ubiquitin Thiolesterase*/metabolism , Ubiquitin Thiolesterase*/genetics , Repressor Proteins*/metabolism , Repressor Proteins*/genetics , Protein Binding* , DNA-Binding Proteins*/metabolism , DNA-Binding Proteins*/genetics, Humans ; Animals ; Mice ; Enhancer Elements, Genetic ; HEK293 Cells ; PHD Zinc Fingers ; Histones/metabolism
مستخلص: The human methyltransferase and transcriptional coactivator MLL4 and its paralog MLL3 are frequently mutated in cancer. MLL4 and MLL3 monomethylate histone H3K4 and contain a set of uncharacterized PHD fingers. Here, we report a novel function of the PHD2 and PHD3 (PHD2/3) fingers of MLL4 and MLL3 that bind to ASXL2, a component of the Polycomb repressive H2AK119 deubiquitinase (PR-DUB) complex. The structure of MLL4 PHD2/3 in complex with the MLL-binding helix (MBH) of ASXL2 and mutational analyses reveal the molecular mechanism which is conserved in homologous ASXL1 and ASXL3. The native interaction of the Trithorax MLL3/4 complexes with the PR-DUB complex in vivo depends solely on MBH of ASXL1/2, coupling the two histone modifying activities. ChIP-seq analysis in embryonic stem cells demonstrates that MBH of ASXL1/2 is required for the deubiquitinase BAP1 recruitment to MLL4-bound active enhancers. Our findings suggest an ASXL1/2-dependent functional link between the MLL3/4 and PR-DUB complexes.
(© 2024. The Author(s).)
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معلومات مُعتمدة: K99 CA241301 United States CA NCI NIH HHS; R00 CA241301 United States CA NCI NIH HHS; AG067664 U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
المشرفين على المادة: 0 (Tumor Suppressor Proteins)
EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
EC 3.4.19.12 (Ubiquitin Thiolesterase)
0 (BAP1 protein, human)
EC 2.1.1.43 (MLL4 protein, human)
0 (Repressor Proteins)
0 (DNA-Binding Proteins)
0 (KMT2C protein, human)
0 (ASXL2 protein, human)
0 (ASXL1 protein, human)
0 (Histones)
تواريخ الأحداث: Date Created: 20240607 Date Completed: 20240607 Latest Revision: 20240617
رمز التحديث: 20240617
مُعرف محوري في PubMed: PMC11161652
DOI: 10.1038/s41467-024-49391-x
PMID: 38849395
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-024-49391-x