دورية أكاديمية
أعرض في EDS

TAD border deletion at the Kit locus causes tissue-specific ectopic activation of a neighboring gene.

التفاصيل البيبلوغرافية
العنوان: TAD border deletion at the Kit locus causes tissue-specific ectopic activation of a neighboring gene.
المؤلفون: Kabirova E; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia., Ryzhkova A; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia., Lukyanchikova V; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia., Khabarova A; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia., Korablev A; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia., Shnaider T; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia., Nuriddinov M; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia., Belokopytova P; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia.; Novosibirsk State University, Novosibirsk, Russia., Smirnov A; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia., Khotskin NV; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia., Kontsevaya G; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia., Serova I; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia., Battulin N; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia. battulin@gmail.com.; Novosibirsk State University, Novosibirsk, Russia. battulin@gmail.com.
المصدر: Nature communications [Nat Commun] 2024 May 28; Vol. 15 (1), pp. 4521. Date of Electronic Publication: 2024 May 28.
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: Proto-Oncogene Proteins c-kit*/genetics , Proto-Oncogene Proteins c-kit*/metabolism , Mast Cells*/metabolism , Melanocytes*/metabolism , Fibroblasts*/metabolism , Chromatin*/metabolism , Chromatin*/genetics, Animals ; Mice ; Vascular Endothelial Growth Factor Receptor-2/genetics ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; Promoter Regions, Genetic/genetics ; Enhancer Elements, Genetic/genetics ; Receptor, Platelet-Derived Growth Factor alpha/genetics ; Receptor, Platelet-Derived Growth Factor alpha/metabolism ; Epigenesis, Genetic ; Genetic Loci ; Mice, Inbred C57BL ; Organ Specificity/genetics ; Gene Editing ; Ectopic Gene Expression ; Male
مستخلص: Topologically associated domains (TADs) restrict promoter-enhancer interactions, thereby maintaining the spatiotemporal pattern of gene activity. However, rearrangements of the TADs boundaries do not always lead to significant changes in the activity pattern. Here, we investigated the consequences of the TAD boundaries deletion on the expression of developmentally important genes encoding tyrosine kinase receptors: Kit, Kdr, Pdgfra. We used genome editing in mice to delete the TADs boundaries at the Kit locus and characterized chromatin folding and gene expression in pure cultures of fibroblasts, mast cells, and melanocytes. We found that although Kit is highly active in both mast cells and melanocytes, deletion of the TAD boundary between the Kit and Kdr genes results in ectopic activation only in melanocytes. Thus, the epigenetic landscape, namely the mutual arrangement of enhancers and actively transcribing genes, is important for predicting the consequences of the TAD boundaries removal. We also found that mice without a TAD border between the Kit and Kdr genes have a phenotypic manifestation of the mutation - a lighter coloration. Thus, the data obtained shed light on the principles of interaction between the 3D chromatin organization and epigenetic marks in the regulation of gene activity.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 22-14-00247 Russian Science Foundation (RSF)
المشرفين على المادة: EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
0 (Chromatin)
EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
تواريخ الأحداث: Date Created: 20240528 Date Completed: 20240528 Latest Revision: 20240605
رمز التحديث: 20240605
مُعرف محوري في PubMed: PMC11133455
DOI: 10.1038/s41467-024-48523-7
PMID: 38806452
قاعدة البيانات: MEDLINE
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