On the structure and dynamics of the complex of the nucleosome and the linker histone

Abstract

Several different models of the linker histone (LH)–nucleosome complex have been proposed, but none of them has unambiguously revealed the position and binding sites of the LH on the nucleosome. Using Brownian dynamics-based docking together with normal mode analysis of the nucleosome to account for the flexibility of two flanking 10 bp long linker DNAs (L-DNA), we identified binding modes of the H5-LH globular domain (GH5) to the nucleosome. For a wide range of nucleosomal conformations with the L-DNA ends less than 65 Å apart, one dominant binding mode was identified for GH5 and found to be consistent with fluorescence recovery after photobleaching (FRAP) experiments. GH5 binds asymmetrically with respect to the nucleosomal dyad axis, fitting between the nucleosomal DNA and one of the L-DNAs. For greater distances between L-DNA ends, docking of GH5 to the L-DNA that is more restrained and less open becomes favored. These results suggest a selection mechanism by which GH5 preferentially binds one of the L-DNAs and thereby affects DNA dynamics and accessibility and contributes to formation of a particular chromatin fiber structure. The two binding modes identified would, respectively, favor a tight zigzag chromatin structure or a loose solenoid chromatin fiber.

Structural insights into the histone H1-nucleosome complex

“…S1). Among several computation-based models of the gH1/H5-nucleosome complex (30)(31)(32)46), two of them show similarities to our model in terms of both location and orientation of gH1 in the complex (30,31). In addition, our model is consistent with several other experimental observations.…”

“…In the symmetric class, gH1/gH5 binds to the nucleosomal DNA at the dyad and interacts with both linker DNAs (16,17,27,28). In the asymmetric class, gH1/gH5 binds to the nucleosomal DNA in the vicinity of the dyad axis and to 10 bp (27,(29)(30)(31)(32) or 20 bp (19,29,33,34) of one linker DNA, or is located inside the DNA gyres, where it interacts with histone H2A (35). In addition, Zhou and colleagues also characterized the orientation of gH5 in the gH5-nucleosome complex (29).…”

The chromatin fiber: multiscale problems and approaches

“…This accessory protein consists of a rigid and well-folded globular head linked to a short N-terminal and a long C-terminal domains, both of which are intrinsically disordered and essential for cell regulation [38]. Although all-atom trajectories of the nucleosome-linker histone complex are too costly, the Wade lab has combined docking, Brownian dynamics, and normal mode analysis to simulate the binding to the H5 globular domain in the nucleosome (without core histone tails) [39 • ]. Their studies suggest that H5 can adopt various docking positions near the nucleosome's dyad axis rather than a single symmetric position where it interacts with both linker DNAs as previously observed [40].…”

“…Linker histones (LH) are highly flexible and can adopt various conformations upon binding to nucleosomes [39 • ]. Studies have shown that N-terminal domain of the LH does not have significant effect on the higher-order chromatin organization; however, the intrinsically disordered C-terminal domain can be a crucial factor in chromatin architecture [37].…”

Dependence of the Linker Histone and Chromatin Condensation on the Nucleosome Environment

“…The linker histone (LH) protein, and its sub-variants, also play pivotal roles in the chromatin compaction 9, 10, 11, 12, 13, 14, 15 . The LH protein binds the nucleosome core at its dyad axis, close to both exiting and entering DNA strands.…”