Dynamic chromatin landscape encodes programs for perinatal transition of cardiomyocytes

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Molecular Genetics

Background:

• The perinatal period is critical for cardiomyocyte adaptation to circulatory changes after birth.
• Dysregulation during this transition can lead to heart disease.
• Mechanisms controlling perinatal cardiomyocyte reprogramming remain largely unknown.

Purpose of the Study:

• To elucidate the regulatory mechanisms governing cardiomyocyte transition during the perinatal period.
• To identify key transcription factors and regulatory elements involved in this process.
• To provide a comprehensive resource for cardiac translational research.

Main Methods:

• Genome-wide chromatin accessibility mapping.
• Analysis of transcription-centered long-range chromatin interactions.
• Gene expression profiling in perinatal cardiomyocytes.
• Recompilation of transcriptional programs in induced stem cell-derived cardiomyocytes.

Main Results:

• Identified MEF2 and AP1 as crucial transcription factors for perinatal cardiomyocyte phenotypic changes.
• Discovered thousands of dynamic regulatory elements mediating transcriptional reprogramming via higher-order chromatin architecture.
• Successfully reprogrammed induced stem cell-derived cardiomyocytes to exhibit adult cardiomyocyte-like electrophysiological expression.

Conclusions:

• MEF2 and AP1 are central drivers of cardiomyocyte perinatal reprogramming.
• Dynamic chromatin architecture plays a key role in regulating gene expression during this transition.
• This study provides a valuable regulatory resource for understanding and improving cardiac development and disease research.