The histone H3-H4 tetramer is a copper reductase enzyme
Abstract
Eukaryotic histone H3-H4 tetramers contain a putative copper (Cu 2+ ) binding site at the H3-H3′ dimerization interface with unknown function. The coincident emergence of eukaryotes with global oxygenation, which challenged cellular copper utilization, raised the possibility that histones may function in cellular copper homeostasis. We report that the recombinant Xenopus laevis H3-H4 tetramer is an oxidoreductase enzyme that binds Cu 2+ and catalyzes its reduction to Cu 1+ in vitro. Loss- and gain-of-function mutations of the putative active site residues correspondingly altered copper binding and the enzymatic activity, as well as intracellular Cu 1+ abundance and copper-dependent mitochondrial respiration and Sod1 function in the yeast Saccharomyces cerevisiae . The histone H3-H4 tetramer, therefore, has a role other than chromatin compaction or epigenetic regulation and generates biousable Cu 1+ ions in eukaryotes.
- Authors:
-
[1];
[1];
[2];
[3];
[4];
[2];
[2];
[5];
[2];
[2];
[1];
[3];
[6]
- Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA., Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
- Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
- Institute for Genomics and Proteomics, Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095, USA.
- Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA., UCLA-DOE Institute for Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA 90095, USA.
- Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA.
- Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA., Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095, USA., Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1635750
- Grant/Contract Number:
- FC02-02ER63421
- Resource Type:
- Published Article
- Journal Name:
- Science
- Additional Journal Information:
- Journal Name: Science Journal Volume: 369 Journal Issue: 6499; Journal ID: ISSN 0036-8075
- Publisher:
- American Association for the Advancement of Science (AAAS)
- Country of Publication:
- United States
- Language:
- English
Citation Formats
Attar, Narsis, Campos, Oscar A., Vogelauer, Maria, Cheng, Chen, Xue, Yong, Schmollinger, Stefan, Salwinski, Lukasz, Mallipeddi, Nathan V., Boone, Brandon A., Yen, Linda, Yang, Sichen, Zikovich, Shannon, Dardine, Jade, Carey, Michael F., Merchant, Sabeeha S., and Kurdistani, Siavash K. The histone H3-H4 tetramer is a copper reductase enzyme. United States: N. p., 2020.
Web. doi:10.1126/science.aba8740.
Attar, Narsis, Campos, Oscar A., Vogelauer, Maria, Cheng, Chen, Xue, Yong, Schmollinger, Stefan, Salwinski, Lukasz, Mallipeddi, Nathan V., Boone, Brandon A., Yen, Linda, Yang, Sichen, Zikovich, Shannon, Dardine, Jade, Carey, Michael F., Merchant, Sabeeha S., & Kurdistani, Siavash K. The histone H3-H4 tetramer is a copper reductase enzyme. United States. https://doi.org/10.1126/science.aba8740
Attar, Narsis, Campos, Oscar A., Vogelauer, Maria, Cheng, Chen, Xue, Yong, Schmollinger, Stefan, Salwinski, Lukasz, Mallipeddi, Nathan V., Boone, Brandon A., Yen, Linda, Yang, Sichen, Zikovich, Shannon, Dardine, Jade, Carey, Michael F., Merchant, Sabeeha S., and Kurdistani, Siavash K. Thu .
"The histone H3-H4 tetramer is a copper reductase enzyme". United States. https://doi.org/10.1126/science.aba8740.
@article{osti_1635750,
title = {The histone H3-H4 tetramer is a copper reductase enzyme},
author = {Attar, Narsis and Campos, Oscar A. and Vogelauer, Maria and Cheng, Chen and Xue, Yong and Schmollinger, Stefan and Salwinski, Lukasz and Mallipeddi, Nathan V. and Boone, Brandon A. and Yen, Linda and Yang, Sichen and Zikovich, Shannon and Dardine, Jade and Carey, Michael F. and Merchant, Sabeeha S. and Kurdistani, Siavash K.},
abstractNote = {Eukaryotic histone H3-H4 tetramers contain a putative copper (Cu 2+ ) binding site at the H3-H3′ dimerization interface with unknown function. The coincident emergence of eukaryotes with global oxygenation, which challenged cellular copper utilization, raised the possibility that histones may function in cellular copper homeostasis. We report that the recombinant Xenopus laevis H3-H4 tetramer is an oxidoreductase enzyme that binds Cu 2+ and catalyzes its reduction to Cu 1+ in vitro. Loss- and gain-of-function mutations of the putative active site residues correspondingly altered copper binding and the enzymatic activity, as well as intracellular Cu 1+ abundance and copper-dependent mitochondrial respiration and Sod1 function in the yeast Saccharomyces cerevisiae . The histone H3-H4 tetramer, therefore, has a role other than chromatin compaction or epigenetic regulation and generates biousable Cu 1+ ions in eukaryotes.},
doi = {10.1126/science.aba8740},
journal = {Science},
number = 6499,
volume = 369,
place = {United States},
year = {Thu Jul 02 00:00:00 EDT 2020},
month = {Thu Jul 02 00:00:00 EDT 2020}
}
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1126/science.aba8740
https://doi.org/10.1126/science.aba8740
Other availability
Search WorldCat to find libraries that may hold this journal
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Solvent Mediated Interactions in the Structure of the Nucleosome Core Particle at 1.9Å Resolution
journal, June 2002
- Davey, Curt A.; Sargent, David F.; Luger, Karolin
- Journal of Molecular Biology, Vol. 319, Issue 5
Thermodynamic Stability of Histone H3 Is a Necessary but not Sufficient Driving Force for its Evolutionary Conservation
journal, January 2011
- Ramachandran, Srinivas; Vogel, Lisa; Strahl, Brian D.
- PLoS Computational Biology, Vol. 7, Issue 1
Histone H3 N-terminal mutations allow hyperactivation of the yeast GAL1 gene in vivo.
journal, September 1992
- Mann, R. K.; Grunstein, M.
- The EMBO Journal, Vol. 11, Issue 9
Contribution of disulfide bonds to the conformational stability and catalytic activity of ribonuclease A: Disulfide bonds of ribonuclease A
journal, January 2000
- Klink, Tony A.; Woycechowsky, Kenneth J.; Taylor, Kimberly M.
- European Journal of Biochemistry, Vol. 267, Issue 2
Metalloproteins Containing Cytochrome, Iron–Sulfur, or Copper Redox Centers
journal, March 2014
- Liu, Jing; Chakraborty, Saumen; Hosseinzadeh, Parisa
- Chemical Reviews, Vol. 114, Issue 8
The bioinorganic chemistry of the ancient ocean: the co-evolution of cyanobacterial metal requirements and biogeochemical cycles at the Archean–Proterozoic boundary?
journal, December 2003
- Saito, Mak A.; Sigman, Daniel M.; Morel, François M. M.
- Inorganica Chimica Acta, Vol. 356
Subcellular redistribution and mitotic inheritance of transition metals in proliferating mouse fibroblast cells
journal, January 2013
- McRae, Reagan; Lai, Barry; Fahrni, Christoph J.
- Metallomics, Vol. 5, Issue 1
HistoneHits: A database for histone mutations and their phenotypes
journal, February 2009
- Huang, H.; Maertens, A. M.; Hyland, E. M.
- Genome Research, Vol. 19, Issue 4
Activation of Cu,Zn-Superoxide Dismutase in the Absence of Oxygen and the Copper Chaperone CCS
journal, June 2009
- Leitch, Jeffry M.; Jensen, Laran T.; Bouldin, Samantha D.
- Journal of Biological Chemistry, Vol. 284, Issue 33
Electron transfer pathways in cytochrome c oxidase
journal, October 2011
- Lucas, M. Fátima; Rousseau, Denis L.; Guallar, Victor
- Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1807, Issue 10
Identification of the Copper Regulon in Saccharomyces cerevisiae by DNA Microarrays
journal, August 2000
- Gross, Claudia; Kelleher, Mark; Iyer, Vishwanath R.
- Journal of Biological Chemistry, Vol. 275, Issue 41
New Insights into the Coordination Chemistry and Molecular Structure of Copper(II) Histidine Complexes in Aqueous Solutions
journal, March 2006
- Mesu, J. Gerbrand; Visser, Tom; Soulimani, Fouad
- Inorganic Chemistry, Vol. 45, Issue 5
Interactions of Nickel(II) with Histones. Stability and Solution Structure of Complexes with CH3CO-Cys-Ala-Ile-His-NH2, a Putative Metal Binding Sequence of Histone H3
journal, July 1995
- Bal, Wojciech; Lukszo, Jan; Jezowska-Bojczuk, Malgorzata
- Chemical Research in Toxicology, Vol. 8, Issue 5
Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae
journal, July 1998
- Longtine, Mark S.; Mckenzie III, Amos; Demarini, Douglas J.
- Yeast, Vol. 14, Issue 10
Determining Thermodynamic Parameters from Isothermal Calorimetric Isotherms of the Binding of Macromolecules to Metal Cations Originally Chelated by a Weak Ligand †
journal, January 2008
- Hong, Lian; Bush, William D.; Hatcher, Lanying Q.
- The Journal of Physical Chemistry B, Vol. 112, Issue 2
Preparation of nucleosome core particle from recombinant histones
book, January 1999
- Luger, Karolin; Rechsteiner, Thomas J.; Richmond, Timothy J.
- Methods in Enzymology
TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions
journal, January 2013
- Kim, Daehwan; Pertea, Geo; Trapnell, Cole
- Genome Biology, Vol. 14, Issue 4
ACE1 regulates expression of the Saccharomyces cerevisiae metallothionein gene.
journal, July 1988
- Thiele, D. J.
- Molecular and Cellular Biology, Vol. 8, Issue 7
Elevated Copper Remodels Hepatic RNA Processing Machinery in the Mouse Model of Wilson's Disease
journal, February 2011
- Burkhead, Jason L.; Ralle, Martina; Wilmarth, Phillip
- Journal of Molecular Biology, Vol. 406, Issue 1
Three new dominant drug resistance cassettes for gene disruption inSaccharomyces cerevisiae
journal, October 1999
- Goldstein, Alan L.; McCusker, John H.
- Yeast, Vol. 15, Issue 14
Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells
journal, May 2012
- Spinazzi, Marco; Casarin, Alberto; Pertegato, Vanessa
- Nature Protocols, Vol. 7, Issue 6
COSMIC: exploring the world's knowledge of somatic mutations in human cancer
journal, October 2014
- Forbes, Simon A.; Beare, David; Gunasekaran, Prasad
- Nucleic Acids Research, Vol. 43, Issue D1
Chromatin Disassembly Mediated by the Histone Chaperone Asf1 Is Essential for Transcriptional Activation of the Yeast PHO5 and PHO8 Genes
journal, June 2004
- Adkins, Melissa W.; Howar, Susan R.; Tyler, Jessica K.
- Molecular Cell, Vol. 14, Issue 5
Oxygen-induced maturation of SOD1: a key role for disulfide formation by the copper chaperone CCS
journal, June 2004
- Furukawa, Yoshiaki; Torres, Andrew S.; O'Halloran, Thomas V.
- The EMBO Journal, Vol. 23, Issue 14
A zinc-finger like metal binding site in the nucleosome
journal, March 2007
- Adamczyk, Małgorzata; Poznański, Jarosław; Kopera, Edyta
- FEBS Letters, Vol. 581, Issue 7
Beyond the Michaelis-Menten equation: Accurate and efficient estimation of enzyme kinetic parameters
journal, December 2017
- Choi, Boseung; Rempala, Grzegorz A.; Kim, Jae Kyoung
- Scientific Reports, Vol. 7, Issue 1
Consequences of Copper Accumulation in the Livers of the Atp7b−/− (Wilson Disease Gene) Knockout Mice
journal, February 2006
- Huster, Dominik; Finegold, Milton J.; Morgan, Clinton T.
- The American Journal of Pathology, Vol. 168, Issue 2
Crystal structure of the nucleosome core particle at 2.8 Å resolution
journal, September 1997
- Luger, Karolin; Mäder, Armin W.; Richmond, Robin K.
- Nature, Vol. 389, Issue 6648
SAMMate: a GUI tool for processing short read alignments in SAM/BAM format
journal, January 2011
- Xu, Guorong; Deng, Nan; Zhao, Zhiyu
- Source Code for Biology and Medicine, Vol. 6, Issue 1
Novel Role of Antioxidant-1 (Atox1) as a Copper-dependent Transcription Factor Involved in Cell Proliferation
journal, February 2008
- Itoh, Shinichi; Kim, Ha Won; Nakagawa, Osamu
- Journal of Biological Chemistry, Vol. 283, Issue 14
Structure–function studies of histone H3/H4 tetramer maintenance during transcription by chaperone Spt2
journal, June 2015
- Chen, Shoudeng; Rufiange, Anne; Huang, Hongda
- Genes & Development, Vol. 29, Issue 12
Selection of chromosomal DNA libraries using a multiplex CRISPR system
journal, August 2014
- Ryan, Owen W.; Skerker, Jeffrey M.; Maurer, Matthew J.
- eLife, Vol. 3
Copper-Binding Motifs: Structural and Theoretical Aspects
journal, May 2003
- Kaufman Katz, Amy; Shimoni-Livny, Liat; Navon, Oshrit
- Helvetica Chimica Acta, Vol. 86, Issue 5
Copper-mediated repression of the activation domain in the yeast Mac1p transcription factor
journal, May 1997
- Graden, J. A.; Winge, D. R.
- Proceedings of the National Academy of Sciences, Vol. 94, Issue 11
Structure of histone-based chromatin in Archaea
journal, August 2017
- Mattiroli, Francesca; Bhattacharyya, Sudipta; Dyer, Pamela N.
- Science, Vol. 357, Issue 6351
Evidence for Cu(II) Reduction as a Component of Copper Uptake by Saccharomyces cerevisiae
journal, January 1995
- Hassett, Richard; Kosman, Daniel J.
- Journal of Biological Chemistry, Vol. 270, Issue 1
Metal Ion Chaperone Function of the Soluble Cu(I) Receptor Atx1
journal, October 1997
- Pufahl, R. A.
- Science, Vol. 278, Issue 5339
A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae
journal, January 1990
- Schmitt, Mark E.; Brown, Timothy A.; Trumpower, Bernard L.
- Nucleic Acids Research, Vol. 18, Issue 10
Designer deletion strains derived fromSaccharomyces cerevisiae S288C: A useful set of strains and plasmids for PCR-mediated gene disruption and other applications
journal, January 1998
- Baker Brachmann, Carrie; Davies, Adrian; Cost, Gregory J.
- Yeast, Vol. 14, Issue 2
Structure of the Histone Chaperone Asf1 Bound to the Histone H3 C-Terminal Helix and Functional Insights
journal, February 2007
- Agez, Morgane; Chen, Jun; Guerois, Raphaël
- Structure, Vol. 15, Issue 2
Using peptide arrays to define nuclear carrier binding sites on nucleoporins
journal, August 2006
- Cushman, Ian; Palzkill, Timothy; Moore, Mary Shannon
- Methods, Vol. 39, Issue 4
Influence of Copper−Sulfur Covalency and Copper−Copper Bonding on Valence Delocalization and Electron Transfer in the Cu A Site of Cytochrome c Oxidase ‖
journal, January 1997
- Williams, Kendra Rose; Gamelin, Daniel R.; LaCroix, Louis B.
- Journal of the American Chemical Society, Vol. 119, Issue 3
Editorial: Introductory Remarks on the General Application of Antisense RNAs and Ribozymes
journal, April 1993
- Rossi, John J.
- Methods, Vol. 5, Issue 1
Imaging of the intracellular topography of copper with a fluorescent sensor and by synchrotron x-ray fluorescence microscopy
journal, August 2005
- Yang, L.; McRae, R.; Henary, M. M.
- Proceedings of the National Academy of Sciences, Vol. 102, Issue 32
Undetectable Intracellular Free Copper: The Requirement of a Copper Chaperone for Superoxide Dismutase
journal, April 1999
- Rae, T. D.
- Science, Vol. 284, Issue 5415
Histones and metal-binding domains
journal, December 1986
- Saavedra, R.
- Science, Vol. 234, Issue 4783
Charting the travels of copper in eukaryotes from yeast to mammals
journal, September 2012
- Nevitt, Tracy; Öhrvik, Helena; Thiele, Dennis J.
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1823, Issue 9
The Saccharomyces cerevisiae copper transport protein (Ctr1p). Biochemical characterization, regulation by copper, and physiologic role in copper uptake.
journal, October 1994
- Dancis, A.; Haile, D.; Yuan, D. S.
- Journal of Biological Chemistry, Vol. 269, Issue 41
X-ray absorption studies of yeast copper metallothionein.
journal, June 1988
- George, G. N.; Byrd, J.; Winge, D. R.
- Journal of Biological Chemistry, Vol. 263, Issue 17
The Role of Glutathione in Copper Metabolism and Toxicity
journal, April 1989
- Freedman, J. H.; Ciriolo, M. R.; Peisach, J.
- Journal of Biological Chemistry, Vol. 264, Issue 10