ING4和ING5对于基H3氨酸14的乙化和心上细胞谱系的发展至关重要
Sophia Y Y Mah1,2, Hannah K Vanyai1,2, Connie S N Li-Wai-Suen1,2
1Walter and Eliza Hall Institute of Medical Research, Epigenetics and Development Division, Melbourne, VIC 3052, Australia.
概括
增长抑制剂4 (ING4) 和5 (ING5) 蛋白对胚胎发育和心脏形成至关重要. 它们的缺失会导致严重的发育缺陷,包括心脏异常和胚胎发育失败.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 增长抑制剂 (ING) 蛋白4和5 (ING4,ING5) 是基因素乙烯转移酶复合体内的染色素结合蛋白.
- 与ING蛋白相互作用的KAT6A/KAT6B基因的突变与人类心脏缺陷有关.
- 在胚胎发育,特别是心脏发育中,ING4和ING5的具体作用仍然在很大程度上不明.
研究的目的:
- 研究ING4和ING5在胚胎发育和心脏形成中的功能.
- 确定ING4和ING5缺乏对心脏发育和相关细胞过程的影响.
主要方法:
- 产生和分析Ing4和Ing5淘汰赛小鼠模型 (Ing5-/-, Ing4-/-Ing5-/-).
- 对胚胎发育的评估,重点关注胆合和心脏形态.
- 对基因素乙化水平 (H3K14ac,H3K23ac) 和基因表达的分析,包括发育和心表基因.
- 对表心细胞种群,心肌紧缩和冠状动脉血管结构的评估.
主要成果:
- 英格兰5-/-小鼠表现出孤立的心室室隔膜缺陷.
- 英格4-/-英格5-/-胚胎在胚胎8.5日出现发育停滞,原因是胆合并失败.
- 这些胚胎表现出减少的素14和素23的基因组 H3 和受损的发育基因表达.
- 胚胎第12.5天的Ing4+/-Ing5-/-心脏具有较少的上心细胞,缺陷的心肌紧缩和冠状动脉血管问题.
- 在ING4/ING5缺陷状态下观察到细胞粘附基因表达和前皮心外生长的缺陷.
结论:
- ING4和ING5对于胚胎发育至关重要,包括正确的胆合和心脏形成.
- ING4和ING5对于确定心上表皮细胞命运和促进心上表皮衍生的细胞群至关重要.
- 人类ING5基因的突变可能是孤立的心室隔膜缺陷的潜在原因.
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