ZFIN ID: ZDB-PUB-081121-18
Nlz1/Znf703 acts as a repressor of transcription
Nakamura, M., Choe, S.K., Runko, A.P., Gardner, P.D., and Sagerström, C.G.
Date: 2008
Source: BMC Developmental Biology   8: 108 (Journal)
Registered Authors: Choe, Seong-Kyu, Nakamura, Mako, Runko, Alexander, Sagerström, Charles
Keywords: none
MeSH Terms:
  • Animals
  • Binding Sites
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Embryo, Mammalian/metabolism
  • HeLa Cells
  • Histone Deacetylases/genetics
  • Histone Deacetylases/metabolism
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Protein Structure, Tertiary
  • Repressor Proteins/genetics
  • Repressor Proteins/metabolism*
  • Transcription, Genetic*
  • Transfection
  • Transgenes
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Zinc Fingers/genetics
PubMed: 19014486 Full text @ BMC Dev. Biol.
BACKGROUND: Members of the NET subfamily of zinc-finger proteins are related to the Sp-family of transcription factors and are required during embryogenesis. In particular, Nlz1/Znf703 and Nlz2/Znf503 are required for formation of rhombomere 4 of the vertebrate hindbrain. While NET family proteins have been hypothesized to regulate transcription, it remains unclear if they function as activators or repressors of transcription. RESULTS: Here we demonstrate that Nlz proteins repress transcription both in cell lines and in developing zebrafish embryos. We first use standard cell culture-based reporter assays to demonstrate that Nlz1/Znf703 represses transcription of a luciferase reporter in four different cell lines. Structure-function analyses and pharmacological inhibition further reveal that Nlz1-mediated repression requires histone deacetylase activity. We next generate a stable transgenic zebrafish reporter line to demonstrate that Nlz1 promotes histone deacetylation at the transgenic promoter and repression of transgene expression during embryogenesis. Lastly, taking a genetic approach we find that endogenous Nlz proteins are required for formation of hindbrain rhombomere 4 during zebrafish embryogenesis by repressing expression of non-rhombomere 4 genes. CONCLUSIONS: We conclude that Nlz1/Znf703 acts as a repressor of transcription and hypothesize that other NET family members function in a similar manner.