mNOTCH1 coactivator complex positively regulates transcription of Hey1, Hey2 and Heyl

Stable Identifier
R-MMU-2065441
Type
Reaction [omitted]
Species
Mus musculus
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General
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mNOTCH1 coactivator complex positively regulates transcription of Hey1, Hey2 and Heyl

Promoters of Hey1, Hey and Heyl genes contain conserved RBPJ (CSL) binding sites. Cotransfection experiments in mouse fibroblast cell line NIH3T3, human embryonic kidney cell line HEK293 and African green monkey kidney cell line COS-7 showed that a recombinant mouse NICD1 activates transcription of a reporter luciferase gene fused to promoters of either mouse Hey1, Hey2 or Heyl. NICD1-mediated transcriptional activation is lost when RBPJ sites in Hey1 promoter are deleted by PCR-directed mutagenesis (Maier and Gessler 2000). Combined loss of Hey1 and Hey2 results in embryonic death of mouse embryos after embryonic day 9.5 with a global lack of vascular remodeling and massive hemorrhage. Similar vascular defects are observed in Jag1 and Notch1 knockout mice, implicating Hey1 and Hey2 as essential transducers of Notch signals in cardiovascular development and in mediation of arterial cell fate decisions (Fischer et al. 2004). Heyl is strongly expressed in the presomitic mesoderm, somites, peripheral nervous system and arterial smooth muscles of mouse embryos. Heyl expression in nascent somites is lost in Notch1 and Dll1 knockout mice, implicating Heyl as a Notch effector during somite formation (Leimeister et al. 2000).

Literature References
PubMed ID Title Journal Year
10964718 Comparative analysis of the human and mouse Hey1 promoter: Hey genes are new Notch target genes

Maier, MM, Gessler, M

Biochem Biophys Res Commun 2000
11044625 Analysis of HeyL expression in wild-type and Notch pathway mutant mouse embryos

Leimeister, C, Schumacher, N, Steidl, C, Gessler, M

Mech Dev 2000
15107403 The Notch target genes Hey1 and Hey2 are required for embryonic vascular development

Fischer, A, Schumacher, N, Maier, M, Sendtner, M, Gessler, M

Genes Dev 2004
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