A highly basic histone H4 domain bound to the sharply bent region of nucleosomal DNA

Abstract

A nucleosomal core particle is composed of two each of histones H2A, H2B, H3 and H4 located inside the particle with approximately 47 base pairs (bp) of DNA wrapped around the octamer in about 1.8 turns of a left-handed superhelix. The path of the superhelix is not smooth; the DNA is sharply bent, or kinked, at positions symmetrically disposed at a distance of about one and four double-helical turns in both directions from the nucleosomal dyad axis (designated as sites +/- 1 and +/- 4 respectively). This non-uniform bending is considered archetypal to other DNA-protein complexes, but its mechanism is not clear (reviewed in ref. 4). DNA-histone chemical cross-linking within the core particle has revealed strong binding of each of the two histone H4 molecules to DNA at a distance of 1.5 helical turns either side of the nucleosomal dyad axis (sites +/- 1.5). In each of these sites, a single flexible domain of H4 was previously shown to contact three points, at about nucleotides 55 and 65 on one strand and nucleotide 88 on the complementary strand, numbering from the 5' terminus of each 147-base strand; these three locations are closely juxtaposed across the highly compressed minor and major grooves (Fig. 1). Here we report that the amino-acid residue of histone H4 cross-linked at the 1.5 site is histidine-18, embedded in a highly basic cluster Lys-Arg-His-Arg-Lys-Val-Leu-Arg which is probably involved in the sharp bending of the DNA double helix at the +/- 1 sites.

Nucleosome Structural Transition during Chromatin Unfolding Is Caused by Conformational Changes in Nucleosomal DNA

“…4), which are very close to the sharply bent regions of the nucleosomal DNA (51-55). Histone H4 cross-links to the sites around Ϯ 1 mainly through the single highly basic domain (30,56,57), which may alter DNA structure in this region (57,58). On the other hand, the change in nucleosomal DNA conformation induced by low ionic strength in isolated core particles or by the stretching of linker DNA during chromatin unfolding can in turn affect histone interactions with these DNA sites.…”

“…Identification of nucleotide-tagged histone H4 peptides (56,57) and selective proteolysis of cross-linked core particles by trypsin and clostripain (30) have demonstrated that histone H4 cross-links via His-18 to three major sites, at nucleotides 57, 66, and 93, which are extended over 1.2 helical turns of the nucleosomal DNA (Fig. 4).…”

Role of Nuclear Matrix in Estrogen Regulated Gene Expression in Human Breast Cancer Cells

“…The chromatin fiber is organized into loops where the base of the loop (MAR) is attached to nuclear matrix proteins (10,44,45). The chromatin loop may have one or several genes.…”

The effects of DNA intercalators on chromatin of chicken red blood cells --- differential extraction on nonhistone proteins

“…Furthermore all detectable variants of DNA conformation are very sensitive to change of energ y state created by alteration of .the negative supercoiling den sity within a close DNA domain [5] . T here are substantial evidences suggesting that most ( if not all ) DNA-binding reagents ( including proteins) can change conformation of the interacting DNA region directly or indirectly by altering the density of the overall supercoiling of the close DNA domain or molecule [6][7][8].…”