RESUMEN
The perinatal period occurring immediately before and after birth is critical for cardiomyocytes because they must change rapidly to accommodate the switch from fetal to neonatal circulation after birth. This transition is a well-orchestrated process, and any perturbation leads to unhealthy cardiomyocytes and heart disease. Despite its importance, little is known about how this transition is regulated and controlled. Here, by mapping the genome-wide chromatin accessibility, transcription-centered long-range chromatin interactions and gene expression in cardiomyocytes undergoing perinatal transition, we discovered two key transcription factors, MEF2 and AP1, that are crucial for driving the phenotypic changes within the perinatal window. Thousands of dynamic regulatory elements were found in perinatal cardiomyocytes and we show these elements mediated the transcriptional reprogramming through an elegant chromatin high-order architecture. We recompiled transcriptional program of induced stem cell-derived cardiomyocytes according to our discovered network, and they showed adult cardiomyocyte-like electrophysiological expression. Our work provides a comprehensive regulatory resource of cardiomyocytes perinatal reprogramming, and aids the gap-filling of cardiac translational research.
RESUMEN
Epidemiological studies have assessed the association between excision repair cross-complementing group 2 (ERCC2) Lys751Gln and Asp312Asn polymorphisms and melanoma risk with conflicting results. Relevant articles were searched from PubMed, Embase, and Web of Science with a time limit of 3 September 2016. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. We performed this meta-analysis with 12 studies including 6157 cases and 8873 controls for Lys751Gln and nine studies including 5037 cases and 7542 controls for Asp312Asn polymorphism. Overall, no significant associations were found under all the models for Lys751Gln polymorphism, and significant associations were found for Asp312Asn polymorphism for AA versus GG (OR=1.12, 95% CI=1.00-1.26) and for the recessive model (OR=1.11, 95% CI=1.00-1.24). In the stratification analyses by source of control: for Lys751Gln polymorphism, significant associations were found for CC versus AA (OR=1.19, 95% CI=1.04-1.36) and the recessive model (OR=1.15, 95% CI=1.02-1.30); for Asp312Asn polymorphism, significant associations were found for AA versus GG (OR=1.31, 95% CI=1.11-1.53) and the recessive model (OR=1.29, 95% CI=1.11-1.50). This meta-analysis suggested that both the Lys751Gln and Asp312Asn polymorphisms were risk factors for melanoma risk in population-based subgroup.