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Review
. 2015 Mar 25;115(6):2255-73.
doi: 10.1021/cr500373h. Epub 2014 Dec 12.

Nucleosome structure and function

Robert K McGinty  1 , Song Tan  1
Affiliations
Review

Nucleosome structure and function

Robert K McGinty et al. Chem Rev. .
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Nucleosome core particle structure and the histone-fold heterodimers. (a) Nucleosome core particle structure (PDB ID 1KX5). Histones and DNA are depicted in cartoon and sticks representations, respectively, and colored as indicated. (b) H3/H4 histone-fold heterodimer. (c) H2A/H2B histone-fold heterodimer. Structures (top) and schemes (bottom) with secondary structure elements indicated. All molecular graphics in this review were prepared using PyMOL software (The PyMOL Molecular Graphics System, version 1.6, Schrodinger, LLC). All structures of NCP using high-resolution structure (PDB ID 1KX5) unless indicated otherwise.
Figure 2
Figure 2
Histone octamer constructed with four helix bundles. (a) Nucleosome core particle structure highlighting H3–H3 four helix bundle (blue). Remainder of H3 and H4 are shown in light blue and light green, respectively. (b) Nucleosome core particle structure highlighting one H4–H2B four helix bundle (green for H4 and red for H2B). Remainder of H4 and H2B are shown in light green and pink, respectively.
Figure 3
Figure 3
Histone-fold heterodimers in the nucleosome core particle structure. (a) Nucleosome core particle structure with central H3/H4 histone-fold tetramer shown in blue (H3) and green (H4). H3 and H4 extensions are shown in light blue and light green, respectively. (b) Nucleosome core particle structure with one H2A/H2B histone-fold dimer shown in yellow (H2A) and red (H2B). H2A and H2B extensions are shown in light yellow and pink, respectively.
Figure 4
Figure 4
Histone-fold heterodimers form a ramp for nucleosomal DNA. (a) H2A/H2B histone-fold heterodimers interact with DNA in two different parallel planes. Structure of NCP viewed from opposite dyad, highlighting H2A and H2B in yellow and red, respectively (left) and scheme of DNA planes (right). (b) H3/H4 tetramer forms a diagonal ramp for DNA connecting two parallel planes. Structure of NCP view from dyad (black oval and orange base pair) with H3 and H4 in blue and green, respectively, (left) and scheme of diagonal DNA ramp (right). Arrows point away from central dyad base pair.
Figure 5
Figure 5
Surface topology and charge of the nucleosome core particle. (a) Surface of nucleosome core particle viewed down the DNA superhelical axis in space-filling representation. (b) Surface electrostatic potential of nucleosome core particle contoured from −5 to +5 kT/e calculated with ABPS. Location of acidic patch is indicated.
Figure 6
Figure 6
Scheme of asymmetric and symmetric 601 sequences. Sequences of 601R symmetric, (canonical) 601 asymmetric, and 601L symmetric sequences with H3/H4 TA steps highlighted in red for left half and blue for right half. Nucleosome salt stability values (molar monovalent salt) are listed at right and indicate stability as follows: 601L > 601 > 601R. This trend correlates with the number of H3/H4 TA steps: 601L (6), 601 (4), 601R (2). The dyad position is indicated (purple).
Figure 7
Figure 7
Location of TA steps in 601L nucleosome core particle structure. (a) 601L NCP structure viewed down the DNA superhelical axis with TA steps interacting with H3/H4 and H2A/H2B colored red and orange, respectively. The dyad is indicated (purple). Histones H3, H4, H2A, and H2B are shown in cartoon representation and colored blue, green, yellow, and red, respectively. Nucleosomal DNA is shown as sticks (light blue). (b) Enlarged view showing one H3/H4 heterodimer bound to DNA containing three TA steps (other histones are not shown for clarity purposes). Backbone phosphates bound to the H3/H4 histone folds are shown in space-filling representation as indicated. Secondary structure elements of dimer are shown.
Figure 8
Figure 8
Minimal base stacking in TA and CA compared to other base pair steps. TA, CA, AA, and AT base pair steps colored as follows: T = yellow, A = blue, G = green, C = red. The thymine methyl groups are shown highlighted in space-filling representation (dark yellow), all other non-hydrogen atoms shown in sticks representation. The minimal base stacking and the absence of atoms close to the thymine methyl group permit greater flexibility of the TA and CA base pair steps.
Figure 9
Figure 9
RNA polymerase II blocking by nucleosome positioning sequences. Sequences of NCP601, NCP603, and NCP605 sequences and their reversed counterparts together with ability to block RNA polymerase II. Multiple TA steps bound to the H3/H4 tetramer downstream (red) of the dyad (purple) blocks RNA polymerase II passage as compared with upstream (blue) of the dyad. TA steps bound to the H2A/H2B dimers are shown in orange. The sequence shown for the 601 sequence is the reverse complement of what is shown in Figure 6 to be consistent with ref (73).
Figure 10
Figure 10
DNA end-to-end packing in nucleosome core particle crystals. Three nucleosome core particles from one plane of the high resolution NCP crystal structure (PDB ID 1KX5) colored yellow, red and blue. (a) Full and (b) enlarged views of the alignment of the DNA ends from adjacent NCP in the structure. The DNA end-to-end packing exists in all crystals of the nucleosome core particle on its own.
Figure 11
Figure 11
DNA stretching in nucleosome core particle structures. Cartoon representation of structure of approximately half of the nucleosomal DNA for (a) 146 bp human alpha-satellite (HAS146) (PDB ID 1AOI, blue) and (b) 145 bp 601 (PDB ID 3LZO, red) nucleosome positioning sequences relative to the HAS147 sequence (PDB ID 1KX5, yellow) (top). Stretching of 1 bp is observed at superhelical location (SHL) −2 with the HAS146 sequence and 1 bp each at SHL ± 5 with the 145 bp 601 sequence. SHLs and the dyad = SHL 0 are indicated. The length of DNA wrapped on each side of the NCP for each of the sequences is also shown (bottom).
Figure 12
Figure 12
Nucleosome recognition using the acidic patch arginine-anchor. From top to bottom, structures of RCC1 (PDB ID 3MVD), Sir3 (PDB ID 3TU4), PRC1 (PDB ID 4R8P), LANA peptide (PDB ID 1ZLA), and CENP-C peptide (PDB ID 4INM) bound to the nucleosome core particle. Overview of structures as viewed from opposite the dyad (right) and zoomed view of acidic patch (left) with arginine-anchor in space-filling representation and key H2A residues shown as sticks. Locations of RCC1 switchback loop (1), DNA binding loop (2), and N-terminus (N) and Sir3 loop 3 (3) and N-terminus (N) are indicated. Histones H3, H4, H2A, and H2B are shown in cartoon representation and colored cornflower blue, light green, wheat, and pink, respectively. DNA (light pink) is shown as sticks.
Figure 13
Figure 13
Models of the 30 nm fiber. Orthogonal views perpendicular to the 30 nm fiber axis (top) and down the axis (bottom) of the Richmond two-start model (left), Rhodes one-start model (center) and Li-Zhu tetranucleosome-unit repeat two-start model (right). The sequence of nucleosomes in each model is indicated. In the Richmond model, each sequential pair of nucleosomes across the fiber is colored similarly. For the Rhodes model, all nucleosomes in the same turn of the solenoid are colored similarly. In the Li-Zhu model, each tetranucleosome repeating unit is colored similarly. Unlabeled nucleosomes in the two-start models are not shown in the bottom views for figure clarity. Linker DNA is not present in the Rhodes model but, given the nature of the solenoidal structure, must be bent. The B-form DNA double helix is shown for comparison (far right). All models shown in space-filling representation and scaled as indicated.
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