WBR0323

Author	[[PageAuthor::Serge Korjian M.D. (Reviewed by Alison Leibowitz) (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::General Principles
Prompt	[[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	AnswerA::Methylation
Answer A Explanation	AnswerAExp::Methylation hinders transcription at the level of chromatin templates. Methylation "mutes" chromatin.
Answer B	AnswerB::Phosphorylation
Answer B Explanation	AnswerBExp::Phosphorylation does not make the chromatin transcriptionally active.
Answer C	AnswerC::Acetylation
Answer C Explanation	AnswerCExp::See explanation.
Answer D	AnswerD::Oxidation
Answer D Explanation	AnswerDExp::Oxidation does not make the chromatin transcriptionally active.
Answer E	AnswerE::Dehydrogenation
Answer E Explanation	AnswerEExp::Dehydrogenation does not make the chromatin transcriptionally active.
Right Answer	RightAnswer::C
Explanation	[[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	Approved::Yes
Keyword	WBRKeyword::acetylation, WBRKeyword::histone, WBRKeyword::histones, WBRKeyword::chromatin, WBRKeyword::transcription, WBRKeyword::molecular, WBRKeyword::epigenetics
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