HIC2 regulates isoform switching during maturation of the cardiovascular system

• Published in: Journal of molecular and cellular cardiology 2018-01, Vol.114, p.29-37
• Main Authors: Dykes, Iain M., van Bueren, Kelly Lammerts, Scambler, Peter J.
• Format: Article
• Language: English
• Subjects: Animals; Cardiovascular System - embryology; Cardiovascular System - metabolism; Congenital heart disease; Creatine kinase; Embryo Loss - pathology; Embryonic development; Erythrocytes - metabolism; Fetus - metabolism; Gene Expression Regulation, Developmental; Haemoglobin; Hemoglobins - metabolism; Kruppel-Like Transcription Factors - blood; Kruppel-Like Transcription Factors - metabolism; Mice; Mutation - genetics; Myocytes, Cardiac - metabolism; Myoglobin; Organ Specificity; Protein Isoforms - metabolism; Time Factors; Troponin; Troponin I - metabolism; Tumor Suppressor Proteins - blood; Tumor Suppressor Proteins - metabolism
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/j.yjmcc.2017.10.007

Physiological changes during embryonic development are associated with changes in the isoform expression of both myocyte sarcomeric proteins and of erythrocyte haemoglobins. Cell type-specific isoform expression of these genes also occurs. Although these changes appear to be coordinated, it is unclear how changes in these disparate cell types may be linked. The transcription factor Hic2 is required for normal cardiac development and the mutant is embryonic lethal. Hic2 embryos exhibit precocious expression of the definitive-lineage haemoglobin Hbb-bt in circulating primitive erythrocytes and of foetal isoforms of cardiomyocyte genes (creatine kinase, Ckm, and eukaryotic elongation factor Eef1a2) as well as ectopic cardiac expression of fast-twitch skeletal muscle troponin isoforms. We propose that HIC2 regulates a switching event within both the contractile machinery of cardiomyocytes and the oxygen carrying systems during the developmental period where demands on cardiac loading change rapidly. •HIC2 regulates developmental and cell type-specific isoform switching.•The mouse mutant exhibits precocious embryonic expression of foetal genes.•Definitive-lineage haemoglobins are expressed in primitive-lineage erythrocytes.•Mature isoforms of cardiac genes are precociously expressed.•Skeletal muscle troponin isoforms are expressed in the heart.