How can a nucleosome motor measure DNA length? Kuni H Iwasa* ,# and - - PowerPoint PPT Presentation

How can a nucleosome motor measure DNA length?

Kuni H Iwasa*,# and Ana-Maria Florescu*,§

# National Institutes of Health, Bethesda, MD USA; § SISSA, Trieste, Italy;

* Max Planck Institute for Physics of Complex Systems Dresden, Germany

acknowledgment

For discussion and support of this work, we thank Frank Jülicher and Max Planck Institute for Physics of Complex Systems, where the major part

• f this work was done.

the question

• A class of chromatin remodeling motors

translocates the nucleosome to the center of DNA strand.

• How does it sense the DNA length?

short long

Leschziner 2011

ACF and ISW1a

unquenching

in vitro experiment

Yang et al. 2006

short long

unit steps

Hwang et al 2014

the assumptions

• The rate limiting step is DNA (un)binding,

which depends on fluctuation of DNA.

• interaction between the motor and the chain

can be described by discrete steps.

• the motor dimers have cooperative

interaction between them

dominant mode of chain fluctuation

“breathing”* approximated by a hinge. angular fluctuation θ

* Li, Bustamante, Widom 2000

the spring that holds DNA determines the amplitude of fluctuation in angle 1 2kθh∆θ2i ⇠ kBT kθ length-independent

viscous drag on chain rotation

πηL3Dr 3kBT = ln L 2r + δ δ ≈ −0.7 + O ✓2r L ◆ ζr ≈ πηL3 3 1 ln(L/2r) − 0.7

* Tirado et al. 1984

Rotational diffusion coefficient is give by,* The Einstein relationship leads to the friction coefficient , Dr ζr L r

rotational diffusion of nucleosome?

ζn = 8πηR3 ζn ζr = 24 ✓R L ◆3 · [ln(L/2r) − 0.7] ζn ζr ∼ 0.3 R ≈ 8 nm Approximate the nucleosome with a sphere, The mass of 1 MD leads to . If L=40 nm, and However, this is an underestimation of because nucleosome is elongated in the direction it holds DNA. ζn L R

fluctuation spectrum

If random noise F(t) is ‘white,’ Consider pivoting motion. ζ dy(t) dt = −k y(t) + F(t) Sy(ω) = 2kBT ζ · 1 (k/ζ)2 + ω2 ζr ≈ πηL3 3 1 ln(L/2r) − 0.7 with

the model

Bound ⇌ Unbund Advanced ↓ ↑ µ ν γ γ eigenvector νA = γµ p γ2 + (γ + µ)2 + (γµ/ν)2 rotation rate of the motor:   B U A   =   γ + µ γ γµ/ν  

alternative assignment

short long

U B A

γ γ µ ν νA = γµ p γ2 + (γ + µ)2 + (γµ/ν)2

length dependence of tugging

1 2 3 4 5 0.1 0.2 0.3 0.4 0.5 0.6

chain length L speed ν → ∞ smaller ν

νA = γµ p γ2 + (γ + µ)2 + (γµ/ν)2

µ = 1

γ ∼ (ln(L/2r) − 0.7)/L3

r = 0.1

• short

long

role of dimerization

8 configurations directions of transitions

U U A B

§ §

§ same conf. B the two subunits share a binding site to avoid wasting energy*

*as proposed by Leonard and Narlikar 2015

antisymmetric geometry

is a protein arm stiffer than DNA?

assumed as if it is… is that true?

DNA does not have to be more flexible if:

• the arm is shorter than saturation length
• its distribution is asymmetric with respect

to DNA

sliding mechanism?

sliding mechanism is not addressed here. addressed is how sliding is initiated. compatible with various sliding mechanisms, e.g.

Hota et al 2013 Ludwigsen et al 2013

in vivo relevance ?

Ricci et al., 2015, Cell 160, 1145–1158 Fudenberg & Mirny 2012

conclusions

• A model for sensing the length of DNA

strand is proposed.

• Chain fluctuation can serve as a sensing

mechanism for ACF.

• Details need to be worked out for a more

quantitative description. Gràcies!