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Cardiac-enriched BAF chromatin-remodeling complex subunit Baf60c regulates gene expression programs essential for heart development and function

机译:富含心脏的BAF染色质重塑复杂亚基Baf60c调节心脏发育和功能必不可少的基因表达程序

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How chromatin-remodeling complexes modulate gene networks to control organ-specific properties is not well understood. For example,Baf60c(Smarcd3) encodes a cardiac-enriched subunit of the SWI/SNF-like BAF chromatin complex, but its role in heart development is not fully understood. We found that constitutive loss ofBaf60cleads to embryonic cardiac hypoplasia and pronounced cardiac dysfunction. Conditional deletion ofBaf60cin cardiomyocytes resulted in postnatal dilated cardiomyopathy with impaired contractile function.Baf60cregulates a gene expression program that includes genes encoding contractile proteins, modulators of sarcomere function, and cardiac metabolic genes. Many of the genes deregulated inBaf60cnull embryos are targets of the MEF2/SRF co-factor Myocardin (MYOCD). In a yeast two-hybrid screen, we identified MYOCD as a BAF60c interacting factor; we showed that BAF60c and MYOCD directly and functionally interact. We conclude that Baf60c is essential for coordinating a program of gene expression that regulates the fundamental functional properties of cardiomyocytes.
机译:染色质重塑复合物如何调控基因网络以控制器官特异性特性的方法尚不清楚。例如,Baf60c(Smarcd3)编码SWI / SNF样BAF染色质复合物的富含心脏的亚基,但尚未完全了解其在心脏发育中的作用。我们发现,Baf60的组成型丧失会导致胚胎心脏发育不全和明显的心脏功能障碍。 Baf60cin心肌细胞的有条件缺失导致出生后扩张型心肌病,收缩功能受损.Baf60调节基因表达程序,该程序包括编码收缩蛋白,肌小节功能调节剂和心脏代谢基因的基因。 Baf60cnull胚胎中许多失调的基因是MEF2 / SRF辅助因子心肌素(MYOCD)的靶标。在酵母双杂交筛选中,我们将MYOCD确定为BAF60c相互作用因子。我们证明了BAF60c和MYOCD直接且功能上相互作用。我们得出结论,Baf60c对于协调调节心肌细胞基本功能特性的基因表达程序至关重要。

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