Hop is an unusual homeobox gene that modulates cardiac development.
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.
Chen
Fabian
F
Department of Medicine, University of Pennsylvania Health System, Philadelphia, PA 19104, USA.
Kook
Hyun
H
Milewski
Rita
R
Gitler
Aaron D
AD
Lu
Min Min
MM
Li
Jun
J
Nazarian
Ronniel
R
Schnepp
Robert
R
Jen
Kuangyu
K
Biben
Christine
C
Runke
Greg
G
Mackay
Joel P
JP
Novotny
Jiri
J
Schwartz
Robert J
RJ
Harvey
Richard P
RP
Mullins
Mary C
MC
Epstein
Jonathan A
JA
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
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