RRC ID 12138
Author Yamada-Okabe T, Imamura K, Kawaguchi N, Sakai H, Yamashita M, Matsumoto N.
Title Functional characterization of the zebrafish WHSC1-related gene, a homolog of human NSD2.
Journal Biochem. Biophys. Res. Commun.
Abstract Methylation of specific lysine residues of histone H3 and H4 has been reported to be important in the structuring of chromatin and for the transcription of certain genes. Proteins with SET domains have been shown to methylate specific lysine residues of histone H3 and H4. We isolated a SET domain-containing gene from the zebrafish (Danio rerio). The gene has the highest sequence similarity to human NSD2, also known as Wolf-Hirschhorn syndrome candidate 1 or WHSC1, and therefore, was named DrWhsc1. DrWhsc1 mRNA is expressed in various tissues with the highest level in testis. Morpholino oligonucleotides for the DrWhsc1 gene affected early embryogenesis in zebrafish, such as endbrain enlargement, abnormal cartilage, marked reduction of bone, and incomplete motor neuron formation. Such developmental abnormalities are also observed in Wolf-Hirschhorn syndrome patients and Whsc1-deficient mice. In addition, suppression of the DrWhsc1 gene or defect in the SET domain of DrWhsc1 resulted in impairment of di-methylation of histone H3K36 at early embryogenesis. These results indicate that DrWhsc1 is a functional homolog of WHSC1 and that the SET domain of DrWhsc1 is essential for di-methylation of histone H3K36 in zebrafish.
Volume 402(2)
Pages 335-9
Published 2010-11-12
DOI 10.1016/j.bbrc.2010.10.027
PII S0006-291X(10)01889-9
PMID 20946879
MeSH Animals Embryo, Nonmammalian / metabolism Gene Knockdown Techniques Histone-Lysine N-Methyltransferase / genetics Histone-Lysine N-Methyltransferase / metabolism* Histones / metabolism Humans Male Methylation Protein Structure, Tertiary Repressor Proteins / genetics Repressor Proteins / metabolism Testis / metabolism Tissue Distribution Zebrafish / embryology* Zebrafish / genetics Zebrafish Proteins / genetics Zebrafish Proteins / metabolism*
IF 2.559
Times Cited 3
Zebrafish rw0 (Tg(CM-isl1:GFP))