Elucidating the influence of linker histone variants on chromatosome dynamics and energetics

Nucleic Acids Research
Dustin C Woods, Jeff Weresczczynski

Abstract

Linker histones are epigenetic regulators that bind to nucleosomes and alter chromatin structures and dynamics. Biophysical studies have revealed two binding modes in the linker histone/nucleosome complex, the chromatosome, where the linker histone is either centered on or askew from the dyad axis. Each has been posited to have distinct effects on chromatin, however the molecular and thermodynamic mechanisms that drive them and their dependence on linker histone compositions remain poorly understood. We present molecular dynamics simulations of chromatosomes with the globular domain of two linker histone variants, generic H1 (genGH1) and H1.0 (GH1.0), to determine how their differences influence chromatosome structures, energetics and dynamics. Results show that both unbound linker histones adopt a single compact conformation. Upon binding, DNA flexibility is reduced, resulting in increased chromatosome compaction. While both variants enthalpically favor on-dyad binding, energetic benefits are significantly higher for GH1.0, suggesting that GH1.0 is more capable than genGH1 of overcoming the large entropic reduction required for on-dyad binding which helps rationalize experiments that have consistently demonstrated GH1.0 in on-...Continue Reading

References

Jan 25, 1977·Journal of Molecular Biology·M Noll, R D Kornberg
Dec 1, 1989·Molecular and Cellular Biology·A ShimamuraA Worcel
Jan 25, 1974·Science·A L Olins, D E Olins
Sep 1, 1967·Psychometrika·S C Johnson
Jan 1, 1980·Annual Review of Biochemistry·J D McGhee, G Felsenfeld
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Mar 1, 1985·Physical Review A: General Physics·W G Hoover
May 1, 1999·Journal of Structural Biology·W WriggersJ A McCammon
Dec 29, 2000·Nature·T MisteliD T Brown
Jun 25, 2002·Journal of Molecular Biology·Curt A DaveyTimothy J Richmond
Jul 11, 2003·Nucleic Acids Research·M M Srinivas BharathM R S Rao
Sep 25, 2003·Cell·Akimitsu KonishiYoshihide Tsujimoto
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Nov 30, 2004·Science·Benedetta DorigoTimothy J Richmond
Jun 22, 2005·The Journal of Cell Biology·Thomas J MarescaRebecca Heald
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Feb 8, 2006·Nature Structural & Molecular Biology·David T BrownTom Misteli
May 23, 2006·Nature Structural & Molecular Biology·Frédéric CatezMichael Bustin
Jun 28, 2008·Proceedings of the National Academy of Sciences of the United States of America·Andrew RouthDaniela Rhodes
Jul 3, 2008·The Journal of Physical Chemistry. B·In Suk Joung, Thomas E Cheatham
Jul 29, 2008·Biophysical Journal·René StehrGero Wedemann
Dec 19, 2008·Nature·Noam KaplanEran Segal
May 7, 2010·The Journal of Biological Chemistry·Eric M GeorgeDavid T Brown
May 12, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sajad Hussain SyedStefan Dimitrov
Dec 7, 2010·Nucleic Acids Research·Manu Shubhdarshan ShuklaStefan Dimitrov
Dec 21, 2010·PLoS Genetics·Christine VoglerRobert Schneider
Feb 18, 2011·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Heather J Szerlong, Jeffrey C Hansen
Mar 1, 2011·Nucleic Acids Research·Georgi V PachovRebecca C Wade
Aug 30, 2011·Bioinformatics·José Ramón Lopéz-BlancoPablo Chacón
Apr 17, 2012·Acta Crystallographica. Section D, Biological Crystallography·Willy Wriggers
May 23, 2012·Physical Chemistry Chemical Physics : PCCP·Samuel Genheden, Ulf Ryde
Jun 2, 2012·Epigenetics & Chromatin·Paul B TalbertSteven Henikoff

❮ Previous
Next ❯

Citations

Dec 15, 2020·Journal of Molecular Biology·Jan Huertas, Vlad Cojocaru
Dec 7, 2020·Current Opinion in Structural Biology·Yunhui PengAnna R Panchenko
Feb 21, 2021·Biophysical Journal·Havva Kohestani, Jeff Wereszczynski
Mar 6, 2021·Journal of Molecular Biology·Dustin C WoodsJeff Wereszczynski
Feb 23, 2021·Journal of Molecular Biology·Hao WuGaregin A Papoian
Jul 12, 2021·Current Opinion in Structural Biology·Fanfan HaoJeffrey J Hayes
Sep 4, 2021·Molecular Cell·Yasuhiro ArimuraHironori Funabiki

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR
X-ray

Software Mentioned

cpptraj
py
MMPBSA
AmberTools16
Modeller
Extreme Science and Engineering Discovery Environment ( XSEDE )
Chimera
Situs
AMBER16
NAMD

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.