TY - JOUR
T1 - Extrusion without a motor
T2 - a new take on the loop extrusion model of genome organization
AU - Brackley, C A
AU - Johnson, J
AU - Michieletto, D
AU - Morozov, A N
AU - Nicodemi, M
AU - Cook, P R
AU - Marenduzzo, D
PY - 2018/1/18
Y1 - 2018/1/18
N2 - Chromatin loop extrusion is a popular model for the formation of CTCF loops and topological domains. Recent HiC data have revealed a strong bias in favour of a particular arrangement of the CTCF binding motifs that stabilize loops, and extrusion is the only model to date which can explain this. However, the model requires a motor to generate the loops, and although cohesin is a strong candidate for the extruding factor, a suitable motor protein (or a motor activity in cohesin itself) has yet to be found. Here we explore a new hypothesis: that there is no motor, and thermal motion within the nucleus drives extrusion. Using theoretical modelling and computer simulations we ask whether such diffusive extrusion could feasibly generate loops. Our simulations uncover an interesting ratchet effect (where an osmotic pressure promotes loop growth), and suggest, by comparison to recent in vitro and in vivo measurements, that diffusive extrusion can in principle generate loops of the size observed in the data. Extra View on : C. A. Brackley, J. Johnson, D. Michieletto, A. N. Morozov, M. Nicodemi, P. R. Cook, and D. Marenduzzo "Non-equilibrium chromosome looping via molecular slip-links", Physical Review Letters 119 138101 (2017).
AB - Chromatin loop extrusion is a popular model for the formation of CTCF loops and topological domains. Recent HiC data have revealed a strong bias in favour of a particular arrangement of the CTCF binding motifs that stabilize loops, and extrusion is the only model to date which can explain this. However, the model requires a motor to generate the loops, and although cohesin is a strong candidate for the extruding factor, a suitable motor protein (or a motor activity in cohesin itself) has yet to be found. Here we explore a new hypothesis: that there is no motor, and thermal motion within the nucleus drives extrusion. Using theoretical modelling and computer simulations we ask whether such diffusive extrusion could feasibly generate loops. Our simulations uncover an interesting ratchet effect (where an osmotic pressure promotes loop growth), and suggest, by comparison to recent in vitro and in vivo measurements, that diffusive extrusion can in principle generate loops of the size observed in the data. Extra View on : C. A. Brackley, J. Johnson, D. Michieletto, A. N. Morozov, M. Nicodemi, P. R. Cook, and D. Marenduzzo "Non-equilibrium chromosome looping via molecular slip-links", Physical Review Letters 119 138101 (2017).
KW - Journal Article
U2 - 10.1080/19491034.2017.1421825
DO - 10.1080/19491034.2017.1421825
M3 - Article
C2 - 29300120
SN - 1949-1034
SP - 1
EP - 10
JO - Nucleus
JF - Nucleus
ER -