WBR0323

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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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