Biophysical studies of cholesterol effects on chromatin.
Changes in chromatin structure regulate gene expression and genome maintenance. Molecules that bind to the nucleosome, the complex of DNA and histone proteins, are key modulators of chromatin structure. Previous work indicated that cholesterol, a ubiquitous cellular lipid, may bind to chromatin in vivo, suggesting a potential function for lipids in modulating chromatin architecture. However, the molecular mechanisms of cholesterol's action on chromatin structure have remained unclear. Here, we explored the biophysical impact of cholesterol on nucleosome and chromatin fibers reconstituted in vitro and characterized in silico the cholesterol binding to the nucleosome. Our findings support that cholesterol assists 10 and 30 nm chromatin formation and induces folding of long chromatin fibers as a result of direct interaction of the cholesterol to six nucleosomal binding sites.
Laboratório de Farmacologia Molecular, Departamento de Farmácia, Universidade de Brasília, Brasília, Brazil.
Isabel T G
ITG
Silva
Laboratório de Farmacologia Molecular, Departamento de Farmácia, Universidade de Brasília, Brasília, Brazil.|Laboratório de Biologia Teórica e Computacional, Departamento de Biologia Celular, Universidade de Brasília, Brasília, Brazil.
Vinícius
V
Fernandes
Laboratório de Biologia Teórica e Computacional, Departamento de Biologia Celular, Universidade de Brasília, Brasília, Brazil.
Caio
C
Souza
Laboratório de Biologia Teórica e Computacional, Departamento de Biologia Celular, Universidade de Brasília, Brasília, Brazil gsantos@unb.br treptow@unb.br.
Werner
W
Treptow
Laboratório de Farmacologia Molecular, Departamento de Farmácia, Universidade de Brasília, Brasília, Brazil gsantos@unb.br treptow@unb.br.
Guilherme M
0000-0003-1489-2161
GM
Santos
D001665:Binding Sites; D055592:Biophysical Phenomena; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology*; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism
D002843:Chromatin; D009707:Nucleosomes; D002784:Cholesterol
lipids; molecular biology; physical biochemistry