Nucleosome mobility and the regulation of gene expression: Insights from single-molecule studies.
Nucleosomes at the promoters of genes regulate the accessibility of the transcription machinery to DNA, and function as a basic layer in the complex regulation of gene expression. Our understanding of the role of the nucleosome's spontaneous, thermally driven position changes in modulating expression is lacking. This is the result of the paucity of experimental data on these dynamics, at high-resolution, and for DNA sequences that belong to real, transcribed genes. We have developed an assay that uses partial, reversible unzipping of nucleosomes with optical tweezers to repeatedly probe a nucleosome's position over time. Using the nucleosomes at the promoters of two model genes, Cga and Lhb, we show that the mobility of nucleosomes is modulated by the sequence of DNA and by the use of alternative histone variants, and describe how the mobility can affect transcription, at the initiation and elongation phases.
Faculty of Biology, Technion-Israel Institute of Technology, Haifa, 32000, Israel.
Sergei
S
Rudnizky
Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, 32000, Israel.
Omri
O
Malik
Faculty of Biology, Technion-Israel Institute of Technology, Haifa, 32000, Israel.
Adaiah
A
Bavly
Faculty of Biology, Technion-Israel Institute of Technology, Haifa, 32000, Israel.
Lilach
L
Pnueli
Faculty of Biology, Technion-Israel Institute of Technology, Haifa, 32000, Israel.|Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, 32000, Israel.
Philippa
P
Melamed
Faculty of Biology, Technion-Israel Institute of Technology, Haifa, 32000, Israel.|Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, 32000, Israel.
Ariel
http://orcid.org/0000-0002-9731-6962
A
Kaplan
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D015292:Glycoprotein Hormones, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
C554042:CGA protein, human; D015292:Glycoprotein Hormones, alpha Subunit; D006657:Histones; D009707:Nucleosomes
mobility; nucleosomes; optical tweezers; single molecule biophysics; transcription