Seol Ja-Hwan, Kim Hye-Jin, Yoo Ja-Kyung, Park Hyun-Ju, Cho Eun-Jung
College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
Biochem Biophys Res Commun. 2008 Sep 26;374(3):543-8. doi: 10.1016/j.bbrc.2008.07.084. Epub 2008 Jul 25.
To understand the role of histone H3 sub-domains in chromatin function, 35 histone H3 tandem alanine mutants were generated and tested for their viability and sensitivity to DNA damaging agents. Among 13 non-viable H3 mutants, 6 were mapped around the alphaN helix and preceding tail region. Mutants with individual alanine substitutions in this region were viable but developed multiple sensitivities to DNA damaging agents. The only viable triple mutant, REI49-50A, in the alphaN helix region could not grow when combined with histone chaperone mutations, such as asf1Delta, cac1Delta, or hir1Delta, suggesting that this particular region is important when the histone assembly/disassembly pathway is compromised. In addition, further analysis showed that T45, E50, or F54 of the alphaN helix genetically interacted with a histone chaperone (Asf1) and transcription elongation factors (Paf1 and Hpr1). These results suggest a specific role of the H3 alphaN helix in histone dynamics mediated by histone chaperones, which might be important during transcription elongation.
为了解组蛋白H3亚结构域在染色质功能中的作用，我们构建了35个组蛋白H3串联丙氨酸突变体，并检测了它们的活力以及对DNA损伤剂的敏感性。在13个无法存活的H3突变体中，有6个位于αN螺旋及之前的尾部区域周围。该区域单个丙氨酸替代的突变体是可存活的，但对DNA损伤剂产生了多种敏感性。αN螺旋区域中唯一可存活的三重突变体REI49 - 50A，与组蛋白伴侣突变体（如asf1Δ、cac1Δ或hir1Δ）组合时无法生长，这表明当组蛋白组装/拆卸途径受损时，这个特定区域很重要。此外，进一步分析表明，αN螺旋的T45、E50或F54与组蛋白伴侣（Asf1）和转录延伸因子（Paf1和Hpr1）发生遗传相互作用。这些结果表明H3αN螺旋在组蛋白伴侣介导的组蛋白动态变化中具有特定作用，这在转录延伸过程中可能很重要。
