Genome-wide compendium and functional assessment of in vivo heart enhancers [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 356.7 Foot forces and warfare
• Thông tin xuất bản: Berkeley, Calif. : Oak Ridge, Tenn. : Lawrence Berkeley National Laboratory ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2016
• Mô tả vật lý: Size: Article No. 12923 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260723
• Chủ đề: 1. 60 applied life sciences; 2. Cardiovascular diseases; 3. Epigenomics; 4. Gene regulation; 5. Transcriptional regulatory elements

Tóm tắt

 Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of >
  35 epigenomic data sets from mouse and human pre-and postnatal hearts we created a comprehensive reference of >
  80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs of two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function.