包括MLL3,卡拉宾和氨酸在内的宏分子复合体调节心脏重塑
Roberto Pane1, Loubna Laib1, Karina Formoso1
1Institut des Maladies Métaboliques et Cardiovasculaires, Inserm, Université de Toulouse III-Paul Sabatier, France (R.P., L.L., K.F., M.D.., Y.S.-M., F.B., N.R., H.F., I.S., E.L., F.L., C.C.).
Circulation research
|December 12, 2023
概括
心脏缩包括由表观遗传因素调节的基因重编程. 这项研究发现了一种新的途径,其中氨酸 (CaN) 激活MLL3,一种组分离子甲基转移酶,促进心脏重塑和心力衰竭.
科学领域:
- 心血管生物学 心血管生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子心脏病学分子心脏病学
背景情况:
- 心脏缩是心力衰竭的前体,涉及显著的基因重编程.
- 表观遗传调节和染色质重塑在心脏缩中至关重要,但具体的重塑者尚未完全理解.
研究的目的:
- 调查染色体重塑剂及其调节功能在心脏缩病变的发病过程中的作用.
- 阐明压力诱导的心脏重塑中表观遗传调节的基础分子机制.
主要方法:
- 在心肌细胞和心脏压力 (横向大动脉收缩) 的小鼠模型中使用了免疫沉试验.
- 在成年小鼠心肌细胞染色体上进行了染色体免疫沉,随后进行了测序 (ChIP-seq).
主要成果:
- 在心肌细胞中发现了一种宏分子复合体,涉及氨素 (CaN),卡拉,STK24和MLL3.
- 证明,在心脏应激之后,CaN的激活会导致MLL3脱化和随后的希斯H3氨酸4单甲基化.
- 显示的MLL3在高缩条件下被招募来准与心肌病相关的基因,其敲击减轻了高缩.
结论:
- 揭示了一种新的表观遗传机制,其中CaN直接调节MLL3基因组甲基转移酶活性.
- 确立了这种CaN-MLL3相互作用在过度缩期间促进心脏重塑.
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