دورية أكاديمية
أعرض في EDS

Chromatin Sensing by the Auxiliary Domains of KDM5C Regulates Its Demethylase Activity and Is Disrupted by X-linked Intellectual Disability Mutations.

التفاصيل البيبلوغرافية
العنوان: Chromatin Sensing by the Auxiliary Domains of KDM5C Regulates Its Demethylase Activity and Is Disrupted by X-linked Intellectual Disability Mutations.
المؤلفون: Ugur FS; Chemistry and Chemical Biology Graduate Program, 600 16th St., San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, 600 16th St., San Francisco, CA 94158, USA., Kelly MJS; Department of Pharmaceutical Chemistry, 600 16th St., San Francisco, CA 94158, USA., Fujimori DG; Department of Pharmaceutical Chemistry, 600 16th St., San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, 600 16th St., San Francisco, CA 94158, USA; Quantitative Biosciences Institute, University of California, San Francisco, 600 16th St., San Francisco, CA 94158, USA. Electronic address: danica.fujimori@ucsf.edu.
المصدر: Journal of molecular biology [J Mol Biol] 2023 Jan 30; Vol. 435 (2), pp. 167913. Date of Electronic Publication: 2022 Dec 07.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 2985088R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1089-8638 (Electronic) Linking ISSN: 00222836 NLM ISO Abbreviation: J Mol Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: 1959- : London : Academic Press
مواضيع طبية MeSH: Chromatin*/genetics , Chromatin*/metabolism , Histone Demethylases*/chemistry , Histone Demethylases*/genetics , Histone Demethylases*/metabolism , Mental Retardation, X-Linked*/genetics, Humans ; DNA/chemistry ; DNA/metabolism ; Kinetics ; Mutation ; Nucleosomes/genetics ; Nucleosomes/metabolism ; Protein Binding ; Protein Domains
مستخلص: The H3K4me3 chromatin modification, a hallmark of promoters of actively transcribed genes, is dynamically removed by the KDM5 family of histone demethylases. The KDM5 demethylases have a number of accessory domains, two of which, ARID and PHD1, lie between the segments of the catalytic domain. KDM5C, which has a unique role in neural development, harbors a number of mutations adjacent to its accessory domains that cause X-linked intellectual disability (XLID). The roles of these accessory domains remain unknown, limiting an understanding of how XLID mutations affect KDM5C activity. Through in vitro binding and kinetic studies using nucleosomes, we find that while the ARID domain is required for efficient nucleosome demethylation, the PHD1 domain alone has an inhibitory role in KDM5C catalysis. In addition, the unstructured linker region between the ARID and PHD1 domains interacts with PHD1 and is necessary for nucleosome binding. Our data suggests a model in which the PHD1 domain inhibits DNA recognition by KDM5C. This inhibitory effect is relieved by the H3 tail, enabling recognition of flanking DNA on the nucleosome. Importantly, we find that XLID mutations adjacent to the ARID and PHD1 domains break this regulation by enhancing DNA binding, resulting in the loss of specificity of substrate chromatin recognition and rendering demethylase activity lower in the presence of flanking DNA. Our findings suggest a model by which specific XLID mutations could alter chromatin recognition and enable euchromatin-specific dysregulation of demethylation by KDM5C.
Competing Interests: Conflict of Interest The authors declare that they have no conflicts of interest.
(Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
References: Nat Commun. 2019 Aug 22;10(1):3795. (PMID: 31439846)
Cell Rep. 2018 Feb 27;22(9):2359-2369. (PMID: 29490272)
PLoS Genet. 2010 Nov 24;6(11):e1001221. (PMID: 21124823)
Genes (Basel). 2021 Jul 18;12(7):. (PMID: 34356104)
Hum Mol Genet. 2015 May 15;24(10):2861-72. (PMID: 25666439)
Nat Struct Mol Biol. 2008 Apr;15(4):419-21. (PMID: 18270511)
Nature. 2007 Aug 9;448(7154):718-22. (PMID: 17687328)
iScience. 2022 Jun 09;25(7):104563. (PMID: 35754730)
Biomol NMR Assign. 2008 Jun;2(1):9-11. (PMID: 19636912)
Elife. 2021 Mar 04;10:. (PMID: 33661100)
Nat Commun. 2017 Nov 14;8(1):1489. (PMID: 29138400)
Mol Cell. 2019 Dec 5;76(5):712-723.e4. (PMID: 31733991)
Nucleic Acids Res. 2021 Jul 2;49(W1):W297-W303. (PMID: 34048569)
Methods Enzymol. 2008;448:23-40. (PMID: 19111169)
Hum Mol Genet. 2002 Jun 1;11(12):1409-19. (PMID: 12023983)
Cell Rep. 2017 Oct 3;21(1):47-59. (PMID: 28978483)
Nat Chem Biol. 2016 Jul;12(7):539-45. (PMID: 27214403)
J Biol Chem. 2016 Feb 5;291(6):2631-46. (PMID: 26645689)
Sci Rep. 2017 Jul 5;7(1):4676. (PMID: 28680062)
Pathogenetics. 2010 Feb 02;3(1):2. (PMID: 20181063)
Cell. 2004 Dec 29;119(7):941-53. (PMID: 15620353)
Nature. 2021 Feb;590(7846):498-503. (PMID: 33361816)
Cell. 2007 Mar 23;128(6):1063-76. (PMID: 17320161)
Trends Biochem Sci. 2011 Jul;36(7):364-72. (PMID: 21514168)
Front Mol Neurosci. 2018 Apr 04;11:104. (PMID: 29670509)
Am J Hum Genet. 2005 Feb;76(2):227-36. (PMID: 15586325)
Cell Rep. 2016 Oct 18;17(4):1158-1170. (PMID: 27760318)
Nature. 2006 Jul 6;442(7098):96-9. (PMID: 16728974)
Nature. 2020 Sep;585(7826):609-613. (PMID: 32939087)
Mol Cell. 2016 Jan 21;61(2):247-59. (PMID: 26778125)
Nature. 2007 May 31;447(7144):601-5. (PMID: 17468742)
Elife. 2020 Jan 10;9:. (PMID: 31922488)
Nat Commun. 2015 Feb 17;6:6204. (PMID: 25686748)
Nat Commun. 2021 Sep 6;12(1):5280. (PMID: 34489435)
Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):2752-7. (PMID: 25730864)
Protein Cell. 2014 Nov;5(11):837-50. (PMID: 24952722)
Cell Rep. 2014 Jan 30;6(2):325-35. (PMID: 24412361)
Mol Cell Biol. 2012 Jan;32(2):479-89. (PMID: 22083960)
Cell. 2007 Mar 9;128(5):877-87. (PMID: 17320162)
Hum Mutat. 2006 Apr;27(4):389. (PMID: 16541399)
Nat Commun. 2019 Jan 9;10(1):94. (PMID: 30626866)
Nucleic Acids Res. 2015 May 26;43(10):4868-80. (PMID: 25916846)
Nature. 2006 Jul 6;442(7098):100-3. (PMID: 16728977)
Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19226-31. (PMID: 18048344)
Cell. 2016 Apr 7;165(2):331-42. (PMID: 27058665)
Elife. 2020 Nov 19;9:. (PMID: 33211010)
Cell Rep. 2013 Apr 25;3(4):1071-9. (PMID: 23545502)
Eur J Hum Genet. 2006 May;14(5):583-6. (PMID: 16538222)
iScience. 2021 Jan 20;24(2):102070. (PMID: 33604523)
Molecules. 2018 Oct 12;23(10):. (PMID: 30322003)
ACS Chem Biol. 2021 Feb 23;:. (PMID: 33621062)
Eur J Med Genet. 2014 Mar;57(4):138-44. (PMID: 24583395)
Nature. 2006 Jul 6;442(7098):91-5. (PMID: 16728978)
Science. 2021 Jan 22;371(6527):. (PMID: 33479123)
Nat Commun. 2019 Dec 5;10(1):5540. (PMID: 31804488)
Cell. 2007 Mar 9;128(5):889-900. (PMID: 17320163)
Eur J Hum Genet. 2010 Mar;18(3):330-5. (PMID: 19826449)
Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):. (PMID: 33526675)
Mol Cell. 2007 Mar 23;25(6):801-12. (PMID: 17363312)
Mol Cell. 2010 Apr 23;38(2):179-90. (PMID: 20417597)
Biochem Biophys Res Commun. 2010 May 28;396(2):323-8. (PMID: 20403335)
Elife. 2018 Apr 12;7:. (PMID: 29648537)
Mol Cell Biol. 2007 Oct;27(20):7220-35. (PMID: 17709396)
Nature. 2019 Sep;573(7774):445-449. (PMID: 31485071)
Nat Struct Mol Biol. 2018 Feb;25(2):154-162. (PMID: 29379173)
J Med Genet. 2008 Dec;45(12):787-93. (PMID: 18697827)
Nature. 2009 Jun 11;459(7248):847-51. (PMID: 19430464)
J Hum Genet. 2013 Jul;58(7):439-45. (PMID: 23739122)
Cell. 2007 Mar 23;128(6):1077-88. (PMID: 17320160)
Cell Rep. 2016 Feb 9;14(5):1000-1009. (PMID: 26804915)
Mol Cell. 2020 Jun 4;78(5):903-914.e4. (PMID: 32396821)
Proc Natl Acad Sci U S A. 2020 Jul 21;117(29):16992-17002. (PMID: 32631994)
Cell Rep. 2019 Apr 9;27(2):387-399.e7. (PMID: 30970244)
Nature. 2006 Jul 6;442(7098):86-90. (PMID: 16728976)
معلومات مُعتمدة: R01 CA250459 United States CA NCI NIH HHS; R01 GM114044 United States GM NIGMS NIH HHS; T32 GM145460 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: Histone demethylase; Intrinsically disordered region; NMR; Nucleosome; Reader domain
المشرفين على المادة: 0 (Chromatin)
9007-49-2 (DNA)
EC 1.14.11.- (Histone Demethylases)
EC 1.14.11.- (KDM5C protein, human)
0 (Nucleosomes)
تواريخ الأحداث: Date Created: 20221210 Date Completed: 20230309 Latest Revision: 20231108
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10247153
DOI: 10.1016/j.jmb.2022.167913
PMID: 36495919
قاعدة البيانات: MEDLINE
الوصف
تدمد:1089-8638
DOI:10.1016/j.jmb.2022.167913