Research article
Nlz1/Znf703 acts as a repressor of transcription
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* Corresponding author: Charles G Sagerström charles.sagerstrom@umassmed.edu
- † Equal contributors
1 Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, USA
2 Department of Psychiatry, University of Massachusetts Medical School, Worcester, USA
3 Kyushu University, Faculty of Agriculture, Fukuoka-city, Japan
4 NINDS, National Institutes of Health, Bethesda, USA
BMC Developmental Biology 2008, 8:108 doi:10.1186/1471-213X-8-108
Published: 12 November 2008Abstract
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.
Conclusion
We conclude that Nlz1/Znf703 acts as a repressor of transcription and hypothesize that other NET family members function in a similar manner.