School of Biological Sciences
Reg. No. 200604393R
Research Theme: Molecular Immunology
Research Project Title: Functional Characterization and Physiological Significance of
SETD3
Pricipal Investigator/Supervisor: Asst/Prof I-hsin Su
Co-supervisor/ Collaborator(s) (if any): NA
Project Description
a) Background
SET domain-containing 3 (SETD3) is a lysine methyltransferase (KMTAse) that expresses in
most tissues and cell types including immune cells. Although SETD3 can regulate
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transcriptional activation through methylation of Histone lysine 36 (H3K26) , our
preliminary data show that SETD3 is expressed in the cytosolic compartment in certain
hematopoietic lineage cells. The expression levels of SETD3 in hematopoietic lineage cells
are up-regulated upon cytokine stimulation and down regulated under various stress
conditions. In addition to the SET domain, SETD3 also contains a Rubisco LSMT substrate binding domain in the C-terminus. It allows binding of the protein to substrates not only to
the N-terminal tails of histones, but also the large subunit of the Rubisco holoenzyme
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complex . Given the emerging evidences showing the biologic significance of non -histone
protein methylation, characterization and study of physiologic functions of SETD3 will be
promising and exciting.
b) Proposed work
As setd3 is a newly identified protein lysine methyltransferase, there is only very limited number of
related studies. We will first characterize the expression pattern of setd3 in various hematopoietic
lineage cells. Meanwhile knockdown/overexpression of setd3 in cell lines and conditional setd3 knockout
mice will be established to determine functional implications. Biochemistry approaches will be taken to
identify novel setdt3 substrates other than histone H3K36.
References:
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Chen, Z., Yan, C.T., Dou, Y., Viboolsittiseri, S.S. & Wang, J.H. The role of a newly identified SET
domain-containing protein, SETD3, in oncogenesis. Haematologica 98, 739-743 (2013).
Eom, G.H. et al. Histone methyltransferase SETD3 regulates muscle differentiation. J Biol Chem
286, 34733-34742 (2011).
Kim, D.W., Kim, K.B., Kim, J.Y. & Seo, S.B. Characterization of a novel histone H3K36
methyltransferase setd3 in zebrafish. Biosci Biotechnol Biochem 75, 289-294 (2011).
Wheeler, D.L. et al. Database resources of the National Center for Biotechnology. Nucleic Acids
Research 31, 28-33 (2003).
Supervisor contact:
If you have questions regarding this project, please email the Principal Investigator:
[email protected]
SBS contact and how to apply:
Associate Chair-Biological Sciences (Graduate Studies) : [email protected]
Please apply at the following: http://admissions.ntu.edu.sg/graduate/R-Programs/RWhenYouApply/Pages/R-ApplyOnline.aspx
60 Nanyang Drive, Singapore 637551
Tel: +65 6316 2800, Fax: +65 6791 3856
Website: http://www.sbs.ntu.edu.sg/Pages/Home.aspx