دورية أكاديمية
أعرض في EDS

Cystatin B-deficiency triggers ectopic histone H3 tail cleavage during neurogenesis.

التفاصيل البيبلوغرافية
العنوان: Cystatin B-deficiency triggers ectopic histone H3 tail cleavage during neurogenesis.
المؤلفون: Daura E; Folkhälsan Research Center, 00290 Helsinki, Finland; Medicum, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland., Tegelberg S; Folkhälsan Research Center, 00290 Helsinki, Finland; Medicum, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland., Yoshihara M; Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Stockholm, Sweden., Jackson C; Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland., Simonetti F; Folkhälsan Research Center, 00290 Helsinki, Finland; Medicum, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland., Aksentjeff K; Folkhälsan Research Center, 00290 Helsinki, Finland; Medicum, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland., Ezer S; Folkhälsan Research Center, 00290 Helsinki, Finland; Medicum, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland., Hakala P; Folkhälsan Research Center, 00290 Helsinki, Finland; Medicum, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland., Katayama S; Folkhälsan Research Center, 00290 Helsinki, Finland; Medicum, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Stockholm, Sweden., Kere J; Folkhälsan Research Center, 00290 Helsinki, Finland; Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Stockholm, Sweden; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland., Lehesjoki AE; Folkhälsan Research Center, 00290 Helsinki, Finland; Medicum, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland. Electronic address: anna-elina.lehesjoki@helsinki.fi., Joensuu T; Folkhälsan Research Center, 00290 Helsinki, Finland; Medicum, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland.
المصدر: Neurobiology of disease [Neurobiol Dis] 2021 Aug; Vol. 156, pp. 105418. Date of Electronic Publication: 2021 Jun 05.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Academic Press Country of Publication: United States NLM ID: 9500169 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-953X (Electronic) Linking ISSN: 09699961 NLM ISO Abbreviation: Neurobiol Dis Subsets: MEDLINE
أسماء مطبوعة: Publication: San Diego, CA : Academic Press
Original Publication: Oxford : Blackwell Science, c1994-
مواضيع طبية MeSH: Cystatin B/*deficiency , Histones/*metabolism , Neural Stem Cells/*metabolism , Neurogenesis/*physiology, Animals ; Cells, Cultured ; Cystatin B/genetics ; Epigenesis, Genetic/physiology ; Histones/genetics ; Mice ; Mice, 129 Strain ; Mice, Knockout
مستخلص: Cystatin B (CSTB) acts as an inhibitor of cysteine proteases of the cathepsin family and loss-of-function mutations result in human brain diseases with a genotype-phenotype correlation. In the most severe case, CSTB-deficiency disrupts brain development, and yet the molecular basis of this mechanism is missing. Here, we establish CSTB as a regulator of chromatin structure during neural stem cell renewal and differentiation. Murine neural precursor cells (NPCs) undergo transient proteolytic cleavage of the N-terminal histone H3 tail by cathepsins B and L upon induction of differentiation into neurons and glia. In contrast, CSTB-deficiency triggers premature H3 tail cleavage in undifferentiated self-renewing NPCs and sustained H3 tail proteolysis in differentiating neural cells. This leads to significant transcriptional changes in NPCs, particularly of nuclear-encoded mitochondrial genes. In turn, these transcriptional alterations impair the enhanced mitochondrial respiration that is induced upon neural stem cell differentiation. Collectively, our findings reveal the basis of epigenetic regulation in the molecular pathogenesis of CSTB deficiency.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Cathepsin; Cystatin B; Histone cleavage; Histone clipping; Neural differentiation; Progressive myoclonus epilepsy
المشرفين على المادة: 0 (Cstb protein, mouse)
0 (Histones)
88844-95-5 (Cystatin B)
تواريخ الأحداث: Date Created: 20210608 Date Completed: 20220119 Latest Revision: 20220119
رمز التحديث: 20231215
DOI: 10.1016/j.nbd.2021.105418
PMID: 34102276
قاعدة البيانات: MEDLINE
الوصف
تدمد:1095-953X
DOI:10.1016/j.nbd.2021.105418