Faculty Profile, National Health Research Institutes, Taiwan

Faculty Profiles


Gan-Guang Liou, Ph.D.

Assistant Investigator
Institute of Molecular and Genomic Medicine
bogun@nhri.org.tw

EDUCATION

Ph.D., Institute of Molecular Medicine, National Taiwan University, 2000
M.S., Institute of Agronomy, National Taiwan University, 1991

PROFESSIONAL EXPERIENCES

- Assistant Investigator, Division of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan (2006 present)
- Postdoctoral Fellow (with assistant Professor Tom Walz and Assistant Professor Danesh Moazed), Harvard Medical School, USA (2002 - 2006)
- Postdoctoral Fellow (with Professor Sue Lin-Chao), Academia Sinica, Taiwan (2001 -2002)
-Research Assistant (with Professor Na-Sheng Lin), Academia Sinica, Taiwan (1994 - 1996)
-Teaching Assistant (with Professor Hsin-Kan Wu), National Taiwan University, Taiwan (1990 - 1991)

RESEARCH INTERESTS

Dr. Liou's general research interest is to use a combination of molecular biology, biochemistry, electron microscopy and bioinformatics to elucidate the mechanism underlying the function of large protein assemblies known as macromolecular machines. He is particularly interested in the structure-function relation of protein complexes that are involved in establishing chromosome structure and those that mediate gene activation/transcription. He would be interested in either establishing a new electron microscopy facility or in joining an existing facility. He is also open to collaborations with other group leaders who wish to use electron microscopy to answer specific questions in their own research area.

RESEARCH ACTIVITIES & ACCOMPLISHMENTS

Previoiusly, Dr. Liou worked on the structure of yeast silencing complexes using electron microscopy (EM) and 3D image reconstructruction. Yeast cells contain two histone binding proteins (Sir3 and Sir4) and a histone modifying enzyme (the deacetylase Sir2) that form the basic machinery to assemble silent chromatin domains. These proteins form a complex, called the SIR complex, which binds to nucleosomes and packages chromatin into an inaccessible heterochromatin-like structure. Although a number of observations had suggested that the three proteins form a complex together, such a complex had never been purified before. He developed a system to assemble SIR complex in vitro. Using biochemical, and biophysical studies then determined their interactions with each other and with the conserved amino termini of histones. The most important discoveries based on these studies were described as following.

There has been a long-standing correlation between histone deacetylation and the assembly of transcriptionally silent chromatin domains. In budding yeast, the deacetylation of histone H4 lysine 16 is required for silent chromatin formation. Based on largely genetic studies, it had been suggested that the Sir3 protein specifically binds to a histone H4 tail that is deacetylated at lysine 16. However, previous studies with bacterially produced Sir3 fragments had failed to uncover any specificity for the binding of Sir3 to histone H4 deacetylated at this residue. In contrast, his experiments with native silencing proteins beautifully demonstrate that the deacetylation of histone H4-lysine 16, and not other H4 lysines, is necessary and sufficient to create a binding site for the Sir3 and Sir2/Sir4 silencing proteins. These results provide a biochemical basis for the role of deacetylation in regulating the assembly of silent chromatin. Moreover, Sir2 uses NAD as a co-factor and transfers acetyl groups from its histone substrates to an NAD breakdown product to form a novel compound, O-acetyl-ADP-ribose (AAR). A role for AAR in silencing had remained an exciting possibility, which could not be tested by conventional in vivo approaches. He set out to determine whether AAR regulates the assembly of the SIR complex using the elegant in vitro assembly system he has developed. His results were shown that the assembly reaction containing AAR promotes the association of more copy Sir3 with the Sir2/Sir4 sub-complex and also induces a dramatic structure rearrangement in the complex. This is a very exciting discovery that provides the first biological function for AAR. The implications of this discovery are far reaching as the Sir2 family of enzymes is universally conserved and all perform the same NAD-dependent deacetylation reaction.

SELECTED PUBLICATIONS

1. Onishi M*, Liou, G-G*, Buchberger JR, Walz T and Moazed D. Role of the Conserved Sir3-BAH Domain in Nucleosome Binding and Silent Chromatin Assembly. Mol. Cell. 28: 1015-1028, 2007.

2. Liou G-G, Tanny JC, Kruger RG, Walz T and Moazed D. Assembly of the SIR Complex and Its Regulation by O-Acetyl-ADP-Ribose, a Product of NAD-Dependent Histone Deacetylation. Cell. 121: 515-527, 2005.

3. Liou G-G, Chang, H-Y, Lin C-S and Lin-Chao S. DEAD box RhlB RNA helicase physically associates with exoribonuclease PNPase to degrade doublestranded RNA independent of the degradosome-assembling region of RNase E. J. Biol. Chem. 277: 41157-41162, 2002.

4. She B-R, Liou G-G and Lin-Chao S. Association of the growth arrest-specific protein Gas7 with F-actin induces reorganization of microfilaments and promotes memberane outgrowth. Exp. Cell Res. 273: 34-44, 2002.

5. Liaw S-H, Chen H-Z, Liou G-G and Chua K-Y. Acid-induced polymerization of the group 5 mite allergen from Dermatophagoides pteronyssinus.. Biochem. Biophys. Res. Commun. 285: 308312, 2001.

6. Liou G-G, Jane W-N, Cohen SN, Lin N-S and Lin-Chao S. RNA degradosomes exist in vivo Escherichia coli as multicomponent complexes associated with the cytoplasmic membrane via the N-terminal region of ribonuclease E. Proc. Natl. Acad. Sci. USA. 98: 63-68, 2001.

(*=Corresponding Author)