Three-dimensional chromatin organization in cardiac development and disease

Abstract

Recent technological advancements in the field of chromatin biology have rewritten the textbook on nuclear organization. We now appreciate that the folding of chromatin in the three-dimensional space (i.e. its 3D "architecture") is non-random, hierarchical, and highly complex. While 3D chromatin structure is partially encoded in the primary sequence and thereby broadly conserved across cell types and states, a substantial portion of the genome seems to be dynamic during development or in disease. Moreover, there is growing evidence that at least some of the 3D structure of chromatin is functionally linked to gene regulation, both being modulated by and impacting on multiple nuclear processes (including DNA replication, transcription, and RNA splicing). In recent years, these new concepts have nourished several investigations about the functional role of 3D chromatin topology dynamics in the heart during development and disease. This review aims to provide a comprehensive overview of our current understanding in this field, and to discuss how this knowledge can inform further research as well as clinical practice.

Keywords: CTCF; Chromatin conformation capture; Chromatin organization; Dilated cardiomyopathy; GWAS; Heart development; Heart failure; Hi-C; Lamin A/C.