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

Abstract

Understanding the structural organization of eukaryotic chromatin and its control of gene expression represents one of the most fundamental and open challenges in modern biology. Recent experimental advances have revealed important characteristics of chromatin in response to changes in external conditions and histone composition, such as the conformational complexity of linker DNA and histone tail domains upon compact folding of the fiber. In addition, modeling studies based on highresolution nucleosome models have helped explain the conformational features of chromatin structural elements and their interactions in terms of chromatin fiber models. This minireview discusses recent progress and evidence supporting structural heterogeneity in chromatin fibers, reconciling apparently contradictory fiber models.The 3 billion DNA base pairs of the human genome are densely packed within eukaryotic chromatin, a nucleoprotein complex in which the DNA is wrapped around nucleosomes (see Fig. 1). Nucleosomes and higher order chromatin structures serve essential cellular functions, including condensation of meters-long genomic DNA by several orders of magnitude to enable its packaging into the micrometer-sized cell nucleus and regulation of DNA-directed processes, such as transcription, replication, recombination, and repair through local and dynamic unfolding of chromatin.Whether the higher order structure of nuclear chromatin is organized into a hierarchy of folding states (1) or non-hierarchical fractal geometry (2), previous landmark studies established the nucleosome as the repeating unit of chromatin (Figs.

Structure-driven homology pairing of chromatin fibers: the role of electrostatics and protein-induced bridging

“…3, the fiber torsional rigidity modulus C (which is unfortunately poorly known [75,76]) and the length of interacting fragments, one can assess the strength of the resulting recognition. If it is much larger than the energy of thermal agitation, at close distances the ES recognition can trigger the association of homologous chromatin loci in favor of non-homologous ones.…”

Genome-Wide Prediction of Nucleosome Occupancy in Maize Reveals Plant Chromatin Structural Features at Genes and Other Elements at Multiple Scales

“…Nucleosomes can be positioned along a DNA molecule to form a 10-nm fiber described as "beads-on-a-string," a structure that is visible by electron microscopy (Finch and Klug, 1976;Finch et al, 1977). Models for higher order chromatin organization are rapidly advancing, and views on how to measure and interpret chromatin fiber structural data are varied and controversial (Lieberman-Aiden et al, 2009;Li and Reinberg, 2011;Mirny, 2011;Nishino et al, 2012;Schlick et al, 2012).…”

Micro- and nanofluidic technologies for epigenetic profiling

“…At physiological ion concentrations, the secondary chromatin contains uneven proportions of both type of structures ("heteromorphic fibers"). 35,38 Furthermore, more recent evidence suggests that even the regular 30-nm fiber structure does not exist consistently in living mammalian cells. 37,41,42 Hence, our current understanding of chromatin structure suggests that the chromatin in a cell exists in a melt-like dynamic state, providing greater accessibility for biological purposes than the conventional static model.…”

“…2(a)). 38 However, the higher-order structure that the primary chromatin strand coils into is still actively debated. 35 A regularly arranged secondary structure known as the "30 nm fiber" is believed to exist.…”