Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
U.S. Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA.
Cell Rep. 2022 Sep 20;40(12):111400. doi: 10.1016/j.celrep.2022.111400.
Heart disease is associated with re-expression of key transcription factors normally active only during prenatal development of the heart. However, the impact of this reactivation on the regulatory landscape in heart disease is unclear. Here, we use RNA-seq and ChIP-seq targeting a histone modification associated with active transcriptional enhancers to generate genome-wide enhancer maps from left ventricle tissue from up to 26 healthy controls, 18 individuals with idiopathic dilated cardiomyopathy (DCM), and five fetal hearts. Healthy individuals have a highly reproducible epigenomic landscape, consisting of more than 33,000 predicted heart enhancers. In contrast, we observe reproducible disease-associated changes in activity at 6,850 predicted heart enhancers. Combined analysis of adult and fetal samples reveals that the heart disease epigenome and transcriptome both acquire fetal-like characteristics, with 3,400 individual enhancers sharing fetal regulatory properties. We also provide a comprehensive data resource (http://heart.lbl.gov) for the mechanistic exploration of DCM etiology.
心脏病与关键转录因子的重新表达有关，这些转录因子在心脏的产前发育过程中才会活跃。然而，这种重新激活对心脏病调节景观的影响尚不清楚。在这里，我们使用 RNA-seq 和针对与活性转录增强子相关的组蛋白修饰的 ChIP-seq，从多达 26 名健康对照者、18 名特发性扩张型心肌病（DCM）患者和 5 名胎儿心脏的左心室组织中生成全基因组增强子图谱。健康个体具有高度可重复的表观基因组景观，包含超过 33000 个预测的心脏增强子。相比之下，我们观察到在 6850 个预测的心脏增强子中，活动存在可重复的疾病相关变化。成人和胎儿样本的联合分析表明，心脏病的表观基因组和转录组都获得了胎儿样特征，有 3400 个单独的增强子具有胎儿的调节特性。我们还提供了一个全面的数据集资源（http://heart.lbl.gov），用于探索 DCM 病因的机制。
Zotero 插件
