English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

In eukaryotic cells, genomic DNA is highly packaged into chromatin to fit inside the nucleus. The accessibility of DNA is dependent on the packing density of chromatin fibers, which plays a critical role in transcriptional regulation and all other DNA-related biological processes. Understanding the structure of chromatin is key to illuminating the functions and molecular mechanisms of chromatin dynamics in epigenetic regulation. The structure of nucleosome—the basic unit of chromatin—has been defined by crystal X-ray studies at high resolution; it consists of 147 base pairs (bp) of DNA wrapping around an octamer of histones (two copies each of H2A, H2B, H3 and H4) approximately 1.7 times (Luger et al., 1997). Despite considerable efforts during the last three decades, however, how the nucleosomes interact with each other in a “beads-on-a-string” nucleosomal array to form a condensed 30-nm chromatin fiber—typically regarded as the secondary structure of chromatin—still remains controversial (Robinson and Rhodes, 2006). Based on the studies of native 30-nm fibers in nuclei or isolated from nuclei by electron microscopy, small angle X-ray/neutron scattering, optical dichroism and analytical centrifugation (Finch and Klug, 1976; Gerchman and Ramakrishnan, 1987; Ghirlando and Felsenfeld, 2008; Langmore and Paulson, 1983; Widom and Klug, 1985), two basic classes of structural models had been proposed in which nucleosomes are either arranged linearly in a one-start solenoid-type helix with bent linker DNA or zigzag back and forth in a two-start stack of nucleosomes connected by a relatively straight DNA linker (Widom and Klug, 1985; Williams et al., 1986; Woodcock et al., 1984). However, it is very difficult to resolve nucleosomes and linker DNA to trace the paths of nucleosomal arrays under conditions in nuclei or in isolated native chromatins in these early studies; in addition, the heterogeneous properties of nucleosomes in native chromatin with different DNA sequences/linker lengths and different histone compositions/modifications make it difficult to define the detailed structure of chromatin fibers. The problem has been partially addressed by reconstituting chromatin fibers in vitro on regular tandem repeats of unique nucleosome-positioning DNA sequences with purified histone proteins (Dorigo et al., 2004), which greatly improved the reproducibility and uniformity for structural analysis and allowed for a dissection of the contribution of individual factors, such as different NRLs, linker histones and histone variants/modifications. Using this system, the 3D cryo-EM structures of 30-nm chromatin fibers reconstituted in vitro from arrays of 12 nucleosomes in the presence of linker histone H1 have been recently determined at resolution of about 11 Å, which clearly show a histone H1-dependent left-handed twist of the repeating tetra-nucleosomal structural units (Song et al., 2014). The structures constitute the largest fragments of chromatin solved at this resolution which is high enough to allow clearly defining the spatial location of all individual nucleosomes and tracing the path of linker DNA, and provide new insights into the helical structure of 30-nm chromatin fibers.

New insights into the helical structure of 30-nm chromatin fibers