Hop Is an Unusual Homeobox Gene that Modulates Cardiac Development

• Published in: Cell Vol. 110; no. 6; pp. 713 - 723
• Main Authors: Chen, Fabian, Kook, Hyun, Milewski, Rita, Gitler, Aaron D., Lu, Min Min, Li, Jun, Nazarian, Ronniel, Schnepp, Robert, Jen, Kuangyu, Biben, Christine, Runke, Greg, Mackay, Joel P., Novotny, Jiri, Schwartz, Robert J., Harvey, Richard P., Mullins, Mary C., Epstein, Jonathan A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.09.2002
• Subjects: 3T3 Cells; Amino Acid Motifs; Amino Acid Sequence; Animals; Conserved Sequence; COS Cells; DNA-Binding Proteins - metabolism; Gene Expression Regulation, Developmental; Genes, Homeobox; Heart - anatomy & histology; Heart - embryology; Heart - growth & development; Heart - physiology; Homeobox Protein Nkx-2.5; Homeodomain Proteins - chemistry; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Homeodomain Proteins - physiology; Mice; Mice, Transgenic; Molecular Sequence Data; Myocardium - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Promoter Regions, Genetic; Sequence Alignment; Serum Response Factor - metabolism; Trans-Activators - genetics; Transcription Factors; Xenopus Proteins; Zebrafish - embryology; Zebrafish - genetics; Zebrafish Proteins - chemistry; Zebrafish Proteins - genetics; Zebrafish Proteins - physiology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(02)00932-7

Hop is a small, divergent homeodomain protein that lacks certain conserved residues required for DNA binding. Hop gene expression initiates early in cardiogenesis and continues in cardiomyocytes throughout embryonic and postnatal development. Genetic and biochemical data indicate that Hop functions directly downstream of Nkx2-5. Inactivation of Hop in mice by homologous recombination results in a partially penetrant embryonic lethal phenotype with severe developmental cardiac defects involving the myocardium. Inhibition of Hop activity in zebrafish embryos likewise disrupts cardiac development and results in severely impaired cardiac function. Hop physically interacts with serum response factor (SRF) and inhibits activation of SRF-dependent transcription by inhibiting SRF binding to DNA. Hop encodes an unusual homeodomain protein that modulates SRF-dependent cardiac-specific gene expression and cardiac development.