Transcriptome profiling of control and Zmynd8-cKO mouse cardiomyocyte

Appropriate gene expression within cardiomyocytes is coordinated by chromatin factors and is essential for heart function. We investigated the role of the chromatin reader ZMYND8 in the mouse heart using null and conditional knockouts (Zmynd8-cKO). While full-length Zmynd8 is not required for cardiomyocyte development, Zmynd8-cKO mice develop cardiomegaly, decreased cardiac function, and premature death compared to controls. Transcriptome analysis of Zmynd8-cKO cardiomyocytes reveals illegitimate expression of transcripts and proteins normally limited to skeletal muscle and integration of TNNI2 skeletal troponin into cardiac sarcomeres of mutant mice. We conclude that ZMYND8 is necessary to maintain appropriate cardiomyocyte homeostasis and gene expression. Transcriptome profiles of 2 replicates of isolated cardiomyocytes from Myh6-CreTg/0 female mice, 2 replicates of isolated cardiomyocytes from Myh6-CreTg/0; Zmynd8fl/fl female mice, and 2 replicates of isolated cardiomyocytes from Myh6-CreTg/0; Zmynd8fl/fl male mice心肌细胞内的适宜基因表达受染色质因子协同调控，对心脏功能至关重要。我们利用全基因敲除（null knockout）与条件性基因敲除（Zmynd8-cKO）模型，探究了染色质读取蛋白（chromatin reader）ZMYND8在小鼠心脏中的功能。尽管全长ZMYND8并非心肌细胞发育所必需，但与对照组相比，Zmynd8-cKO小鼠会出现心脏肥大、心功能减退及过早死亡的表型。对Zmynd8-cKO心肌细胞的转录组分析显示，突变小鼠中出现了本应仅局限于骨骼肌的转录本与蛋白质的异位表达，且其心肌肌节内可见骨骼肌肌钙蛋白TNNI2的整合。本研究表明，ZMYND8是维持心肌细胞稳态与适宜基因表达所必需的。本数据集包含三类样本的转录组图谱：来自Myh6-CreTg/0雌性小鼠的分离心肌细胞的2个生物学重复、来自Myh6-CreTg/0; Zmynd8fl/fl雌性小鼠的分离心肌细胞的2个生物学重复，以及来自Myh6-CreTg/0; Zmynd8fl/fl雄性小鼠的分离心肌细胞的2个生物学重复。