title: Hop is an unusual homeobox gene that modulates cardiac development.
abstract: 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.
authors.affiliation: Department of Medicine, University of Pennsylvania Health System, Philadelphia, PA 19104, USA.
authors.forename: Fabian
authors.initials: F
authors.lastname: Chen
authors.forename: Hyun
authors.initials: H
authors.lastname: Kook
authors.forename: Rita
authors.initials: R
authors.lastname: Milewski
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Gitler
authors.forename: Min Min
authors.initials: MM
authors.lastname: Lu
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Ronniel
authors.initials: R
authors.lastname: Nazarian
authors.forename: Robert
authors.initials: R
authors.lastname: Schnepp
authors.forename: Kuangyu
authors.initials: K
authors.lastname: Jen
authors.forename: Christine
authors.initials: C
authors.lastname: Biben
authors.forename: Greg
authors.initials: G
authors.lastname: Runke
authors.forename: Joel P
authors.initials: JP
authors.lastname: Mackay
authors.forename: Jiri
authors.initials: J
authors.lastname: Novotny
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schwartz
authors.forename: Richard P
authors.initials: RP
authors.lastname: Harvey
authors.forename: Mary C
authors.initials: MC
authors.lastname: Mullins
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Epstein
mesh_terms: D016475:3T3 Cells; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology* / Q000254:growth & development* / Q000502:physiology; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D026362:Serum Response Factor / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D029867:Xenopus Proteins; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000099251:Myocardin
chemical_list: D004268:DNA-Binding Proteins; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D026362:Serum Response Factor; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D000099251:Myocardin; C466740:Hop protein, mouse; C095552:NKX2-5 protein, human; C484469:Nkx2-5 protein, mouse; C466739:hopx protein, zebrafish