Cross-linker mediated compaction and local morphologies in a model chromosome

Abstract

Chromatin and associated proteins constitute the highly folded structure of chromosomes. We consider a self-avoiding polymer model of the chromatin, segments of which may get cross-linked via protein binders that repel each other. The binders cluster together via the polymer mediated attraction, in turn, folding the polymer. Using molecular dynamics simulations, and a mean field description, we explicitly demonstrate the continuous nature of the folding transition, characterized by unimodal distributions of the polymer size across the transition. At the transition point the chromatin size and cross-linker clusters display large fluctuations, and a maximum in their negative cross-correlation, apart from a critical slowing down. Along the transition, we distinguish the local chain morphologies in terms of topological loops, inter-loop gaps, and zippering. The topologies are dominated by simply connected loops at the criticality, and by zippering in the folded phase. arXiv:1811.08172v2 [cond-mat.soft]

Multivalent binding proteins can drive collapse and reswelling of chromatin in confinement

“…Hence for typical value of T = 300 K, the timescale ranges in between τ = 3 πησ 3 / ϵ ≃ 6 – 60 ms. We performed Langevin dynamics simulation using Velocity-Verlet algorithm [68] with time step δt = 0.002 τ . In our simulation we observed all features of chromatin architecture to appear with CTCF (binder) numbers much less than the experimentally obtained number and within the CTCF density range consistent with experimental data [66] as well as previously reported theoretical studies [32, 40, 41, 44]. Thus even with larger polymer or confinement radius we expect all the features to be present within the biological range of CTCF number inside cell.…”

“…These binders can generate different stable configurations of chromatin polymer through attachment. The chromatin polymer is found to undergo a coil-globule like transition from an open state to folded state as the binder concentration is increased [32,40,41]. The contact probability exponents in these studies are consistent with experimental observations [42].…”

“…The coil-globule transition of chromatin in unconfined space has been well studied in the literature [32, 40, 41, 42, 43, 45, 44]. While studies of confined polymers have shown novel features such as glassy dynamics upon strong confinement [55], effects of confinement on chromatin polymer in presence of chromatin binding proteins is has not been well studied.…”

Multivalent binding proteins can drive collapse and reswelling of chromatin in confinement

“…The chromatin polymer is found to undergo a coil-globule like transition from an open state to folded state as the binder concentration is increased. 39,47,48 The contact probability exponents in these studies are consistent with experimental observations. 49 On the other hand, stiffness of chromatin polymer and switching of binders between 'on' state and 'off' state play an important role in determining the structure of the clusters of chromatin formed by binders, and their kinetics.…”

Impact of crowders on the morphology of bacterial chromosomes

“…The DNA of E. coli is ∼ 5% negatively supercoiled, this undertwisting causing chain warps, folds and braid-like plectoneme structures to appear [6]. Also, cross-linking of (a) E-mail: amit@iopb.res.in (b) E-mail: mulder@amolf.nl (c) E-mail: debc@iopb.res.in different DNA segments by nucleoid associated proteins (NAPs) and loop formation by active structural modification of chromosome (SMC) proteins mediate chromosome compaction [4,5,[7][8][9]. Dedicated proteins converting the looped structures to topologically associated domains (TAD) are also identified [5,[10][11][12].…”