Sun Xin, Hota Swetansu K, Zhou Yu-Qing, Novak Stefanie, Miguel-Perez Dario, Christodoulou Danos, Seidman Christine E, Seidman J G, Gregorio Carol C, Henkelman R Mark, Rossant Janet, Bruneau Benoit G
Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, M5G 1X8 Canada.
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8 Canada.
Biol Open. 2018 Jan 5;7(1):bio029512. doi: 10.1242/bio.029512.
How chromatin-remodeling complexes modulate gene networks to control organ-specific properties is not well understood. For example, () 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 of leads to embryonic cardiac hypoplasia and pronounced cardiac dysfunction. Conditional deletion of in cardiomyocytes resulted in postnatal dilated cardiomyopathy with impaired contractile function. regulates a gene expression program that includes genes encoding contractile proteins, modulators of sarcomere function, and cardiac metabolic genes. Many of the genes deregulated in null 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.
染色质重塑复合物如何调节基因网络以控制器官特异性特性尚不清楚。例如，（）编码一种富含心脏的SWI/SNF样BAF染色质复合物亚基，但其在心脏发育中的作用尚未完全了解。我们发现（）的组成性缺失会导致胚胎心脏发育不全和明显的心脏功能障碍。心肌细胞中（）的条件性缺失导致出生后扩张型心肌病，收缩功能受损。（）调节一个基因表达程序，该程序包括编码收缩蛋白、肌节功能调节剂和心脏代谢基因的基因。在（）基因敲除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，我们鉴定出MYOCD是BAF60c相互作用因子；我们表明BAF60c和MYOCD直接且功能性地相互作用。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。
