The Effect of Internucleosomal Interaction on Folding of the Chromatin Fiber

Abstract

The folding of the nucleosome chain into a chromatin fiber modulates DNA accessibility and is therefore an important factor for the control of gene expression. The fiber conformation depends crucially on the interaction between individual nucleosomes. However, this parameter has not been accurately determined experimentally, and it is affected by posttranslational histone modifications and binding of chromosomal proteins. Here, the effect of different internucleosomal interaction strengths on the fiber conformation was investigated by Monte Carlo computer simulations. The fiber geometry was modeled to fit that of chicken erythrocyte chromatin, which has been examined in numerous experimental studies. In the Monte Carlo simulation, the nucleosome shape was described as an oblate spherocylinder, and a replica exchange protocol was developed to reach thermal equilibrium for a broad range of internucleosomal interaction energies. The simulations revealed the large impact of the nucleosome geometry and the nucleosome repeat length on the compaction of the chromatin fiber. At high internucleosomal interaction energies, a lateral self-association of distant fiber parts and an interdigitation of nucleosomes were apparent. These results identify key factors for the control of the compaction and higher order folding of the chromatin fiber.

Toward Convergence of Experimental Studies and Theoretical Modeling of the Chromatin Fiber

“…In vitro, the formation of such structures is promoted by the same factors as the secondary structure: divalent cations, interactions between core histone N-terminal tails (46,82), LHs (83), and heterochromatin architectural factors such as MENT, MeCP2, and Sir3 (84,85). Modeling shows that longer nucleosome repeats typical of terminally differentiated cells promote lateral self-association of the chromatin fibers and nucleosome interdigitation (74).…”

Electrostatic interactions in biological DNA-related systems

“…With all these complications for analytical modelling in mind, extensive computer simulations of fiber formation performed in recent years, [366][367][368][369][370] provide a comprehensive complementary coverage on several intricate issues. With a growing computer power, nowadays, more fine and important details of NCP structure can be incorporated in largescale fiber simulations, rendering them more instructive and probably superior to analytical, ''model'' calculations with their limited applicability regimes.…”

A Coarse-Grained DNA Model Parameterized from Atomistic Simulations by Inverse Monte Carlo

“…A number of theoretical coarse-graining models of DNA [24][25][26][27][28][29][30][31][32][33][34][35] and chromatin [13][14][15][36][37][38][39][40][41][42][43][44][45][46][47][48][49] have been reported recently. In recent works from the Papoian group, a CG model of a single DNA molecule was developed [24][25][26]50].…”