WBR0323

Author	[[PageAuthor::Serge Korjian M.D. (Reviewed by Alison Leibowitz) (Reviewed by Serge Korjian)]]
Exam Type	USMLE Step 1
Main Category	Genetics
Sub Category	General Principles
Prompt	A researcher, studying the regulation of transcription in mice, shows that core histones undergo molecular changes at particular lysine residues, in order to neutralize their positively charged tail and to decrease their affinity for DNA. These changes enable regulatory proteins to access chromatin templates, which are required for transcription. Which of the following molecular changes is most likely to impact the histones in the researcher's observations?
Answer A	Methylation
Answer A Explanation	Methylation hinders transcription at the level of chromatin templates. Methylation "mutes" chromatin.
Answer B	Phosphorylation
Answer B Explanation	Phosphorylation does not make the chromatin transcriptionally active.
Answer C	Acetylation
Answer C Explanation	See explanation.
Answer D	Oxidation
Answer D Explanation	Oxidation does not make the chromatin transcriptionally active.
Answer E	Dehydrogenation
Answer E Explanation	Dehydrogenation does not make the chromatin transcriptionally active.
Right Answer	C
Explanation	Acetylation of core histones, such as H2A, H2B, H3, and H4, plays a major role in the regulation of transcription in eukaryotic cells. The acetylation of lysine residues at the tails of histones neutralizes its positively charge and decreases its affinity for DNA. Consequently, the alteration of nucleosomal conformation facilitates the transcription at the level of chromatin templates. Educational Objective: Histone acetylation is crucial in the regulation of eukaryotic transcriptional activity. References: Struhl K. Histone acetylation and transcriptional regulatory mechanisms. Genes Dev. 1998;12:599-606.
Approved	Yes
Keyword	acetylation, histone, histones, chromatin, transcription, molecular, epigenetics
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