WDR5与基因组 H3 在 K4 中甲基化相关,对 H3 K4 的甲基化和脊椎动物发育至关重要
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Analysis of Histone Antibody Specificity with Peptide Microarrays
Published on: August 1, 2017
Joanna Wysocka1, Tomek Swigut, Thomas A Milne
1Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10021, USA.
Cell
|June 18, 2005
概括
WD40重复蛋白WDR5识别了基因组H3氨酸4 (K4) 甲基化,这是与基因激活相关的标记. WDR5对于H3K4三甲基化,HOX基因激活和脊椎动物发育至关重要.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 发展生物学 发展生物学
背景情况:
- 基因组H3 lysine 4 (K4) 甲基化是一种关键的表观遗传标记,与真核生物的转录激活有关.
- MLL蛋白家族 (MLL1,MLL2,hSet1) 是参与基因调节的H3 K4甲基转移酶.
研究的目的:
- 研究WD40重复蛋白WDR5在H3K4甲基化中的作用及其功能后果.
- 为了确定WDR5是否能直接识别特定的质子修饰.
主要方法:
- 生物化学测试以评估WDR5与甲基化素H3尾巴和核细胞之间的相互作用.
- 在人类细胞中减少WDR5,以评估其在H3 K4三甲基化和HOX基因表达中的作用.
- 在Xenopus laevis幼中进行功能研究,以评估WDR5.5在发育中的作用.
主要成果:
- WDR5直接与基因组H3二甲基和三甲基化基因组H3在K4结合,以及与H3-K4-二甲基化基因组结合.
- WDR5对于甲基转移酶复合物的招募到K4-二甲基化H3和全球H3K4三甲基化至关重要.
- 人体细胞中WDR5的枯竭导致HOX基因激活受损.
- WDR5对脊椎动物的发育至关重要,其耗尽会导致发育缺陷和Xenopus的改变Hox基因表达.
结论:
- WDR5作为H3 K4甲基化标记的读取器,专门识别二甲基化和三甲基化K4.
- 这种识别机制对于招募H3K4甲基转移酶复合体至关重要,促进基因激活.
- 对于脊椎动物正常发育来说,WDR5是不可或缺的,这突显了这种表观遗传读写机制的保留重要性.
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