PUBLICATION
Bone morphogenetic protein-2 induces expression of murine zinc finger transcription factor ZNF450
- Authors
- Edgar, A.J., Dover, S.L., Lodrick, M.N., McKay, I.J., Hughes, F.J., and Turner, W.
- ID
- ZDB-PUB-110128-14
- Date
- 2005
- Source
- Journal of cellular biochemistry 94(1): 202-215 (Journal)
- Registered Authors
- Keywords
- ID1, N-CoR, SMRT, histone deacetylase, MAZR/ZNF278, myoneurin
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Blotting, Northern
- Bone Morphogenetic Protein 2
- Bone Morphogenetic Proteins/physiology*
- Cell Line
- Mice
- Molecular Sequence Data
- Nucleic Acid Hybridization
- Polymerase Chain Reaction
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Sequence Homology, Amino Acid
- Subtraction Technique
- Transcription Factors/chemistry
- Transcription Factors/physiology*
- Transforming Growth Factor beta/physiology*
- Zinc Fingers
- PubMed
- 15526281 Full text @ J. Cell. Biochem.
Citation
Edgar, A.J., Dover, S.L., Lodrick, M.N., McKay, I.J., Hughes, F.J., and Turner, W. (2005) Bone morphogenetic protein-2 induces expression of murine zinc finger transcription factor ZNF450. Journal of cellular biochemistry. 94(1):202-215.
Abstract
The bone morphogenetic protein-2 (BMP-2) is a potent secreted factor that promotes osteoblast differentiation during development. Exposure to BMP-2 is sufficient to cause a lasting change in cell fate presumably by activating specific target genes. To identify genes downstream of BMP-2 we treated the murine pluripotent embryonic cell line, C3H10T1/2 that can be induced to form an osteoblastic phenotype, with 100 ng/ml BMP-2 for 24 h. Using suppression subtractive hybridisation we found the novel zinc finger transcription factor, ZNF450 was upregulated. The single-copy ZNF450 gene spans 15.6 kb on chromosome 10B1 and consists of seven exons, the first of which is untranslated. The open reading frame encodes a 710 reside protein. Analysis of the protein sequence reveals a highly conserved amino-terminal BTB/POZ dimerisation domain, an AT-hook motif, and eight C2H2 zinc fingers. Library screening identified a second mRNA isoform encoding a short protein isoform with one zinc finger. Using reverse transcriptase-real time PCR to measure mRNA expression we found that ZNF450, Runx2/Cbfa-1, and Sp7/osterix were induced by BMP-2 after 4 h in C2C12 myoblast cells. Treatment of C2C12 cells with BMP-2 causes a shift from a myoblastic to osteoblastic phenotype. ZNF450 was upregulated three to fivefold after 24 h in C3H10T1/2 cells and required 100 ng/ml BMP-2. Expression of the 3 kb major transcript was highest in liver, testis, and kidney. However, ZNF450 mRNA was found also in a wide range of adult tissues. The consistent induction of ZNF450 by BMP-2 after 4 h in three murine pluripotent cell lines suggests that ZNF450 may play a role in the BMP-2 signalling pathway.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping