#histone octamer

Regulation of chromatin structure

How many base pairs of DNA are wrapped around the histone octamer?

Structural biology consensus derived from multiple crystal forms and cryoEM shows nucleosome core particle wraps 146 to 147 base pairs of DNA in 1.65 left-handed superhelical turns around histone octamer disc, creating 14 minor groove contacts. Early nuclease protection assays estimated 146 base pairs resistant to micrococcal digestion. Chromatosome including H1 adds twenty base pairs bringing protection to 167 base pairs. Values 120 base pairs underrepresent wrapped length, 200 equals full repeat with linker, 33 base pairs corresponds roughly to single superhelical turn. This conserved length reflects requirement to bend DNA around octamer while exposing tails for regulation across eukaryotes.

Ref: Luger et al., 1997 2.8 Å Structure; Richmond and Davey 2003: 146-147 bp Wrapped Around Octamer

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Nucleosome Packing

Histone octamer conservation during replication occurs for:

During semi-conservative DNA replication parental histone octamer distribution must conserve epigenetic information. Pulse-chase labeling combined with density gradient shows H3-H4 tetramer (H3-H4)2 remains intact as unit, does not split into dimers, segregating randomly to one of two daughter duplexes behind fork. This allows recycling of parental marks like H3K9 methylation to reestablish heterochromatin on both daughters via reader-writer mechanisms. In contrast H2A-H2B dimers exchange rapidly, mixing old and new, H1 readily dissociates. Therefore H3-H4 tetramer conservation underlies epigenetic inheritance during and after replication.

Ref: Jackson V 1990 Biochemistry; Alberts et al., Molecular Biology of the Cell, Chapter 5: H3-H4 Tetramer Conservation During Replication

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Nucleosome Packing

Number of turns of DNA around histone octamer is:

Quantitation of DNA trajectory around histone octamer shows slightly more than one and half circles. High resolution structures measure 1.65 to 1.67 superhelical turns protecting 147 base pairs, about 83 base pairs per full superhelical turn, creating fourteen histone-DNA contact points via arginine side chains inserted into minor grooves. One turn would protect only 80 base pairs, two full turns would need 166 base pairs which exceeds core length. Value 1.65 explains why linker DNA emerges close together, why H1 can bridge entry exit and sealing two turns, enabling higher order folding into 30 nanometer fiber.

Ref: Luger et al., Nature 1997; Lodish et al., Molecular Cell Biology, 9th ed., 1.65 Turns of DNA

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Nucleosome Packing

DNA wraps around histone octamer in which direction?

DNA path around histone octamer dictates DNA topology. Around octamer DNA follows left-handed superhelical ramp of approximately 1.65 turns, compensating positive supercoiling generated ahead of replication fork. Upon nucleosome assembly on closed circular plasmid, agarose electrophoresis shows plasmid acquires more negative writhe, measured as linking number decrease, directly proving left-handed wrapping. Right-handed wrap would produce positive supercoiling opposite to experimental observation. Random binding would produce no systematic change, zig-zag describes fiber arrangement not wrapping direction. Therefore left-handed orientation established by crystallography and topology.

Ref: Richmond Structure; Alberts et al., Molecular Biology of the Cell, Chapter 5: DNA Wraps Left-handed Around Octamer

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Nucleosome Packing

Length of DNA wrapped around histone octamer is approximately:

Crystallography at 2.8 angstrom resolution reveals 146 to 147 base pairs of B-form DNA make 1.65 left-handed superhelical turns around histone octamer, contacting fourteen arginine anchors inserted into minor grooves. Phosphate backbone sharply bent every 10 base pairs. Earlier digestion estimated about 146 base pairs resistant to micrococcal nuclease. Values of 120 base pairs underrepresent protection, 167 includes linker DNA bound by H1 forming chromatosome, 200 equals full repeat including variable linker. This precise length accounts for linking number change of minus 1.2 per nucleosome enabling topological assays.

Ref: Richmond TJ and Davey CA 2003; NCBI Bookshelf, Chromosomal DNA Packaging: 147 bp Wrapped Around Octamer

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