WBR0541

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Author [[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Alison Leibowitz) (Reviewed by Serge Korjian)]]
Exam Type USMLE Step 1
Main Category Genetics
Sub Category General Principles
Prompt A geneticist studies chromatin structure of sperm by undergoing isolation of various chromatin components. He notes that when he eliminates one tripartite structure, but maintains the nucleosome, the stability of the DNA stem is compromised with increased susceptibility to nuclease digestion. Which of the following chromatin components is most likely eliminated by the geneticist?
Answer A Histone H1
Answer A Explanation Histone H1 is outside the nucleosome core. It provides stability of the DNA stem and prevents the nuclease digestion of the nucleosome.
Answer B Histone H3
Answer B Explanation Histone H3 is a component of the nucleosome.
Answer C DNA backbone
Answer C Explanation The DNA backbone is a component of the nucleosome.
Answer D ATP
Answer D Explanation ATP has no role in the chromatin structure.
Answer E Chromatosome
Answer E Explanation Chromatosome is the combination of nucleosomes and the linking H1 histones.
Right Answer A
Explanation Chromatin is composed of repeated nucleosomes, which are in turn composed of DNA molecules bound to a histone tetramer. Core histones of the nucleosome are H2A, H2B, H3, and H4, all of which are tripartite proteins. These histones have helix-strand-helix motifs on different ends of a long central helix, which form a "helix fold". The H1 histone is also a tripartite protein that is not located in the core nucleosome. It connects two nucleosomes and is referred to as a "linker histone". The combination of the nucleosome (DNA, H2A, H2B, H3, H4) and H1 linker histone is called a chromatosome. The H1 histone and its particular position within the chromatin structure facilitates the nucleosomal stability and protection from nuclease digestion.

Educational Objective: Histone H1, a tripartite protein, is referred to as a linker protein because it links 2 nucleosomes. It provides stability of the DNA stem and prevents nuclease digestion of the nucleosome.
References: Arents G, Burlingame RW, Wang BC, Love WE, Moudrianakis EN. The nucleosomal core histone octamer at 3.1 A resolution: a tripartite protein assemble and a left-handed superhelix. Proc Natl Acad Sci 1991; 88:10148-10152.
Whitlock JP, Simpson RT. Removal of histone H1 exposes a fifty base pair DNA segment between nucleosomes. Biochemistry. 1976; 15:3307-3314.
Harshman SW, Young NL, Parthun MR, Freitas MA. H1 histones: current perspectives and challenges. Nucl Acids Res. 2013; 41(21):9593-609.

Approved Yes
Keyword Histone, Chromatin, Chromatosome, Nucleosome, DNA, H1, Nuclease
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