Charge state of the globular histone core controls stability of the nucleosome.
Presented here is a quantitative model of the wrapping and unwrapping of the DNA around the histone core of the nucleosome that suggests a mechanism by which this transition can be controlled: alteration of the charge state of the globular histone core. The mechanism is relevant to several classes of posttranslational modifications such as histone acetylation and phosphorylation; several specific scenarios consistent with recent in vivo experiments are considered. The model integrates a description based on an idealized geometry with one based on the atomistic structure of the nucleosome, and the model consistently accounts for both the electrostatic and nonelectrostatic contributions to the nucleosome free energy. Under physiological conditions, isolated nucleosomes are predicted to be very stable (38 +/- 7 kcal/mol). However, a decrease in the charge of the globular histone core by one unit charge, for example due to acetylation of a single lysine residue, can lead to a significant decrease in the strength of association with its DNA. In contrast to the globular histone core, comparable changes in the charge state of the histone tail regions have relatively little effect on the nucleosome's stability. The combination of high stability and sensitivity explains how the nucleosome is able to satisfy the seemingly contradictory requirements for thermodynamic stability while allowing quick access to its DNA informational content when needed by specific cellular processes such as transcription.
Fenley
Andrew T
AT
Department of Physics, Virginia Tech, Blacksburg, Virginia, USA.
Adams
David A
DA
Onufriev
Alexey V
AV
D000107:Acetylation; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
D006657:Histones; D009707:Nucleosomes; D004247:DNA
Adv Protein Chem. 1995;46:27-58
7771321
J Chem Phys. 2004 May 15;120(19):9394-400
15267879
Biopolymers. 2001 Jan;58(1):106-15
11072233
Nat Struct Mol Biol. 2005 Jan;12(1):46-53
15580276
Biopolymers. 2007 Feb 5;85(2):115-30
17103419
J Mol Biol. 1984 Jun 15;176(1):77-104
6737480
Biochemistry. 1990 Nov 6;29(44):10219-25
2271649
J Phys Condens Matter. 2006 Apr 12;18(14):S173-S185
19088861
Nat Cell Biol. 2010 Mar;12(3):294-8
20139971
Nature. 2005 Jul 14;436(7048):294-8
16015338
J Mol Biol. 2005 Feb 11;346(1):135-46
15663933
Cell. 2005 May 6;121(3):375-85
15882620
Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1960-5
11854495
J Mol Biol. 2003 Oct 3;332(5):1183-93
14499620
Mol Biol (Mosk). 1983 Jul-Aug;17(4):855-67
6621526
Biochemistry. 2000 Apr 4;39(13):3835-41
10736184
J Mol Biol. 2003 Nov 21;334(2):229-40
14607115
Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W368-71
15980491
Biophys J. 1995 Aug;69(2):380-8
8527651
J Mol Graph. 1996 Feb;14(1):33-8, 27-8
8744570
Biopolymers. 2007 Jun 5;86(2):127-35
17330872
Biophys J. 2002 Jan;82(1 Pt 1):345-56
11751321
Methods Enzymol. 1992;212:400-24
1518457
Biochim Biophys Acta. 1997 Mar 20;1351(1-2):213-22
9116035
DNA Repair (Amst). 2008 Dec 1;7(12):2020-4
18848648
Phys Rev Lett. 2000 Nov 13;85(20):4389-92
11060645
Curr Opin Genet Dev. 2006 Apr;16(2):171-6
16503136
Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3278-83
15728351
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3458-62
20142505
J Am Chem Soc. 2003 Dec 10;125(49):15087-92
14653743
J Biol Chem. 2007 Mar 9;282(10):7632-40
17189264
Biochemistry. 1986 Mar 25;25(6):1421-8
3964683
Nucleic Acids Res. 2007;35(19):6640-7
17913747
Biochemistry. 1994 Aug 9;33(31):9276-84
8049228
Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9000-5
18577595
Methods Enzymol. 2004;375:23-44
14870657
Biophys J. 2004 Jan;86(1 Pt 1):67-74
14695250
J Cell Sci. 1996 Jan;109 ( Pt 1):257-62
8834810
J Mol Biol. 1976 Oct 25;107(2):145-58
1003464
Biophys J. 1995 Oct;69(4):1519-27
8534822
J Biol Chem. 1989 Apr 15;264(11):6515-9
2703503
Science. 1982 Apr 30;216(4545):475-85
7071593
Anal Biochem. 2002 Jul 15;306(2):259-69
12123664
Genetics. 2008 Jun;179(2):793-809
18558650
J Biol Chem. 2009 Jun 12;284(24):16575-16583
19363025
Nat Rev Genet. 2008 Jan;9(1):15-26
18059368
Biochemistry. 2001 Sep 18;40(37):10927-33
11551187
Q Rev Biophys. 1978 May;11(2):103-78
353875
Biochemistry. 2009 Aug 25;48(33):7842-8
19618963
Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10037-41
11517324
J Biomol Struct Dyn. 2004 Oct;22(2):215-26
15317482
Biochemistry. 2004 Jan 27;43(3):736-41
14730978
Cell. 2008 Jul 25;134(2):231-43
18662539
J Mol Biol. 2008 Sep 12;381(4):816-25
18653199
Mol Cell. 2007 Sep 21;27(6):890-900
17889663
Nucleic Acids Res. 1990 May 11;18(9):2739-47
2339060
Biochemistry. 1993 Mar 2;32(8):1895-8
8383529
Phys Rev Lett. 2004 Jun 4;92(22):228101
15245260
Phys Rev E Stat Nonlin Soft Matter Phys. 2002 Jul;66(1 Pt 1):011918
12241395
Biochemistry. 1989 Mar 7;28(5):2271-81
2719953
Biochem Cell Biol. 2005 Aug;83(4):468-76
16094450
Nature. 2003 May 8;423(6936):145-50
12736678
J Mol Biol. 2003 Mar 14;327(1):85-96
12614610
Nucleic Acids Res. 1984 May 25;12(10):4351-9
6728680
Nature. 1997 Sep 18;389(6648):251-60
9305837
J Mol Biol. 1995 Nov 24;254(2):130-49
7490738
Biochemistry. 1982 Jul 6;21(14):3327-34
7115674
Biopolymers. 1977 Jul;16(7):1415-34
880365
Biochemistry. 1993 Oct 12;32(40):10568-79
7691177
Nature. 2009 Apr 2;458(7238):591-6
19234442
Nat Struct Mol Biol. 2004 Nov;11(11):1037-43
15523479
J Phys Condens Matter. 2015 Feb 18;27(6):060301
25563698
Mol Cell. 2005 Apr 1;18(1):123-30
15808514
Expert Rev Proteomics. 2005 Oct;2(5):719-29
16209651
Proteins. 2006 Jun 1;63(4):928-38
16493626