Chang-Hui Shen

Professor and Chair of Biology

College of Staten Island, City University of New York
08/14-present Professor

College of Staten Island, City University of New York
01/08-08/14 Associate Professor

College of Staten Island, City University of New York
09/02-12/07 Assistant Profess

National Institutes of Health, Bethesda, Maryland, USA
04/1998-08/2002 Visiting Fellow

沈昌輝教授

紐約市立大學史坦頓分校生物學系主任

紐約市立大學生物學博士班教授

紐約市立大學生物化學博士班教授

Degrees

BS, National Chung-Hsing University

MS, National Chung-Hsing University

PhD, University of Edinburgh (Scotland)

Scholarship and Publications

(*:undergraduate student; **: graduate student)

Refereed Articles

Konarzewska P**, Sherr GL**, Ahmed S*, Ursomanno B*, Shen CH. (2017) Vma3p protects cells from programmed cell death through the regulation of Hxk2p expression. Biochem Biophys Res Commun. 493, 233-239.

Sherr GL**, LaMassa N**, Li E**, Phillips G, Shen CH. (2017) Pah1p negatively regulates the expression of V-ATPase genes as well as vacuolar acidification. Biochem Biophys Res Commun. 491, 693-700.

Isma Butt*, Andrew Hong*, Jing Di, Sonia Aracena**, Probal Banerjee, Chang-Hui Shen. (2014) The effects of serotonin1A receptor on female mice body weight and food intake are associated with the differential expression of hypothalamic neuropeptides and the GABAA receptor. Neuropeptides. 48, 313-318.

Roshini N Wimalarathna**, Po Yun Pan*, Chang-Hui Shen (2014) Codependent recruitment of Ino80p and Snf2p is required for yeast CUP1 activation. Biochem. Cell Bio. 92, 69-75.

Abdeslem El Idrissi, Chang Hui Shen and William J. L’Amoreaux. (2013) Neuroprotective role of Taurine during aging. Amino Acids. 45, 735-750.

Andrew Hong*, Aiying Zhang**, Yang Ke, Abdeslem El Idrissi and Chang-Hui Shen (2012) Decreased expression of GABAA b Subunits in the Brains of Mice Lacking the Fragile X Mental Retardation Protein. J. Mol. Neurosci. 46, 272-275.

Roshini N. Wimalarathna**, Po Yun Pan* and Chang-Hui Shen (2012) Chromatin repositioning activity and transcription machinery are both recruited by Ace1p in yeast CUP1. Biochem Biophys Res Commun. 422, 658-663.

Paulina Konarzewska**, Michelle Esposito** and Chang-Hui Shen (2012) INO1 induction requires chromatin remodelers Ino80p and Snf2p but not the histone acetylases. Biochem Biophys Res Commun 418, 483-488.

Roshini N. Wimalarathna**, Chen-Han Tsai* and Chang-Hui Shen (2011) Transcriptional regulation of genes involved in yeast phospholipid biosynthesis. J Microbiol 49, 265-273.

Michelle Esposito** Paulina Konarzewska**, Oluwafemi Odeyale*, and Chang-Hui Shen (2010) Activator-dependent recruitment of histone acetylation at the yeast INO1 promoter. Biochem Biophys Res Commun 391, 1285-1290.

Aiying Zhang**, Chang-Hui Shen, Shuang Yong Ma, Yang Ke, and Abdeslem El Idrissi (2009) Altered expression of Autism-associated genes in the brain of Fragile X mouse model. Biochem Biophys Res Commun 379, 920-923.

Jason Ford*, Oluwafemi Odeyale*, and Chang-Hui Shen (2008) Activator-dependent recruitment of SWI/SNF and INO80 during INO1 activation. Biochem Biophys Res Commun. 373, 602-626.

Jason Ford*, Oluwafemi Odeyale*, Antonious Eskandar*, Nafila Kouba*, and Chang-Hui Shen (2007) A SWI/SNF- and INO80-dependent nucleosome movement at the INO1 promoter. Biochem Biophys Res Commun. 361, 974-979.

David Clark and Chang-Hui Shen. (2006) Mapping histone modifications by nucleosome immunoprecipitation. Methods in Enzymology, 410, 416-430.

Geetu Mendiratta , Peter R. Eriksson , Chang-Hui Shen , and David Clark. (2006) The DNA-binding domain of the yeast Spt10 activator includes a zinc finger that is homologous to foamy virus integrase. J. Biol. Chem. 281, 7040-7048.

Peter R. Eriksson, Geetu Mendiratta, Neil McLaughlin, Tyra Wolfsberg, Leopoldo Maríño-Ramirez, Tiffany Pompa*, Mohendra Jainerin*, David Landsman, Chang-Hui Shen and David J. Clark (2005) The putative histone acetyltransferase encoded by the yeast SPT10 gene binds specifically to upstream activating sequences in the major core histone promoters Mol. Cell. Biol. 25, 9127-9137.

Yeonjung Kim, Chang-Hui Shen, and David Clark.(2004) Purification and nucleosome mapping analysis of native yeast plasmid chromatin. Methods. 33, 59-67.

Chang-Hui Shen, Benoit P. Leblanc, Carolyn Neal, Ramin Akhaven and David J. Clark. (2002) Targeted histone acetylation at the yeast CUP 1 promoter requires the transcriptional activator, the TATA boxes, and the putative histone acetylase encoded by SPT10. Mol. Cell. Biol. 22, 6406-6416.

Chang-Hui Shen, Benoit Leblanc, Jennifer Alfieri and David Clark. (2001) Remodeling of the yeast CUP 1 chromatin involves activator-dependent re-positioning of nucleosomes over the entire gene and flanking sequences. Mol. Cell. Biol. 21: 534-547.

Chang-Hui Shen and David Clark, (2001) DNA sequence plays a major role in determining nucleosome positions in yeast chromatin. J. Biol. Chem. 276:35209-3516.

Book

Chang-Hui Shen (2012) Histones: Class, Structure and Function, Nova Science Publisher, Inc. NY. ISBN-13: 978-1-62100-274-1.

Book Chapter

Chang Hui Shen, Eugene Lempert*, Isma Butt*, Lorenz S. Neuwirth**, Xin Yan** and Abdeslem El Idrissi (2013) Changes in gene expression at inhibitory synapses in responses to Taurine treatment. In: Abdeslem El Idrissi and William L’Amoreaux, Taurine 8: Physiological and mechanisms of action, p.p. 187-194, Springer, New York. ISBN-978-1-4614-6129-6.

Chang-Hui Shen (2012) Linker histones and chromatin structure. In: Chang-Hui Shen. Histones: Class, Structure and Function, p.p. 35-57, Nova Science Publisher, Inc. NY. ISBN-13: 978-1-62100-274-1.

Roshini Wimalarathna** and Chang-Hui Shen (2012) Histone modifications and gene expression. In: Chang-Hui Shen. Histones: Class, Structure and Function, p.p. 89-108, Nova Science Publisher, Inc. NY. ISBN-13: 978-1-62100-274-1.

Conference abstracts

Jaclyn DiBello*, Fina Vitale*, Chang-Hui Shen. The Engineering of Truncated INO80 Protein Yeast Mutants to Identify Acetylated Lysine Residues of Histones. CSI undergraduate conference, NY, 2017.

Christine Huynh*, Dilakshi Mampitiya*, Alicia Seecoomar*, Kristina Lam*. Engineering yeast HAT/HDAC mutant strains via homologous recombination. CSI undergraduate conference, NY, 2015.

Dhiwya Alex*, Goldie Sherr**, Chang-Hui Shen. Construction of a Tagged PAH1–HA and OPI1–GFP Yeast Strain needed for determining the interplay between Pah1p and Opi1p in the regulation of UASINO Gene Expression. CSI undergraduate conference, NY, 2015.

Chang-Hui Shen and Michelle Esposito**. A working model of epigenetic regulation in yeast INO1 gene expression. Nature conference: Genomic technologies and biomaterials for understanding disease. San Diego, CA, 2014.

Christine Huynh*, Dilakshi Mampitiya*, Suzanne Ahmed*, Jwala Alex*, Kristi Russo*. Construction and Screening of Yeast Chromatin Remodeler and Histone Acetylase/ Deacetylase Knockout Strains. CSI undergraduate conference, NY, 2014.

Dhiwya Alex*, Christine Samuel*, Ekrem Yetiskul*, Goldie Sherr*, Chang-Hui Shen. Regulation of the Saccharomyces cerevisiae Phosphatidate Phosphatase Encoded by the PAH1 Gene. CSI undergraduate conference, NY, 2014.

Chang-Hui Shen, Michelle Esposito, Paulina Konarzewska. A working model of yeast INO1 activation in which the dissociation of chromatin remodelers might result from acetylation. EMBO Conference on Allosteric interactions in cell signaling and regulation. Pasteur Institute, Paris, France. 2013.

Alina Kogan, Wafa Shakil, Valerie Imaduerie, Aun Syed, Michelle Esposito, and Chang-Hui Shen. Construction of Ino80-FLAG Gcn5p knockout yeast strain to identify novel role of histone acetylases in INO1 transcriptional activation. CSI undergraduate conference, NY, 2013.

Amara Abid, Merlin Raj, Goldie Lazarus, Chang-Hui Shen. The role of Pah1p in the expression of phospholipid biosynthetic pathways. CSI undergraduate conference, NY, 2013.

Isma Butt* and Chang-Hui Shen. The influence of 5-HT1A receptor on the feeding behavior and the expression of hypothalamic neuropeptides. CSI undergraduate conference, NY, 2012.

Eugene Lempert* and Chang-Hui Shen. Cloning of the critical domains of Ino2p responsible for recruiting chromatin remodeling activities. CSI undergraduate conference, NY, 2011.

Roshini Wimalarathna**, Po Yun Pan* and Chang-Hui Shen. (2011) Transcriptional regulation of yeast CUP1 gene. Biochem. Cell Biol. (abstract)

Eugene Lempert* and Chang-Hui Shen. (2011) Cloning of the critical domains of Ino2p responsible for recruiting chromatin remodeling activities. CSI undergraduate conference, NY, 2011.

Roshini Wimalarathna**, Po Yun Pan* and Chang-Hui Shen. Transcriptional regulation of yeast CUP1 gene. 32nd International conference – Asilomar Chromatin and Chromosome Conference. CA, 2010.

Michelle Esposito*, Paulina Konarzewska** and Chang-Hui Shen. Histone acetylation at INO1 promoter requires the transcriptional activator and both Gcn5p and Esa1p histone acetylase. CSI undergraduate conference, NY, 2009.

Jason Ford* and Chang-Hui Shen. SWI/SNF and INO80 Contribute to Local Nucleosome Mobilization at the INO1 Promoter. CSI undergraduate conference, NY, 2008.

Chang-Hui Shen, Jason Ford* and Oluwafemi Odeyale*. The role of romatin remodeling activities in INO1 activation. Symposium on biological complexity: diseases of transcription. Salk Institute, San Diego, CA. 2007.

Tiffany Pompa*, Jonathan Blaize*, William L’Amoreaux and Chang-Hui Shen. Correlation between Methylation and Acetylation within the Cell due to Environmental Factors. Microscopy and Microanalysis 2006 Meeting. Chicago.

Tiffany Pompa*, Jonathan Blaize*, William L’Amoreaux and Chang-Hui Shen. Co-localization of the putative histone acetylase Spt10p and chemically modified histone H3. Microscopy and Microanalysis 2005 Meeting. Honolulu, Hawaii.

Oluwafemi Odeyale* and Chang-Hui Shen. The interplay between histone modifying enzyme and chromatin remodeling complex in INO1 activation. New York City

Louis Strokes Alliance for Minority Participation Conference, Steven’s Institute of Technology in New Jersey, 2005.

Oluwafemi Odeyale* and Chang-Hui Shen. The role of chromatin remodeling complex in yeast INO1 gene expression. National conference & research symposium, 2005, Stony Brook, awarded First Place for poster in the biological sciences.

Oluwafemi Odeyale* and Chang-Hui Shen. The role of chromatin remodeling complex in yeast INO1 gene expression. Annual Biomedical Research Conference for Minority Students, Dallas, TX, 2004, pp.280.

Oluwafemi Odeyale* and Chang-Hui Shen. The role of chromatin remodeling complex in yeast INO1 gene expression. New York City Louis Strokes Alliance for Minority Participation Conference, Brookhaven National Laboratory, 2004.

Antonious Eskandar*, Nafila Kouba*, Oluwafemi Odeyale*, Baishali Kanjilal+ and Chang-Hui Shen. In Vivo Chromatin Remodeling by Yeast Ino80p. The 69th Cold Spring Harbor Symposium on Quantitative Biology. Cold Spring Harbor, NY. 2004, pp.58.

Chang-Hui Shen and David Clark. Histone Hyperacetylation at the CUPI Promoter Requires the Transcriptional Activator and the TATA Boxes. Keystone Symposia - Mechanisms of Eukaryotic Transcriptional Regulation, Santa Fe, NM 2001, pp. 90.

Chang-Hui Shen, Benoit Leblanc, Jennifer Alfieri and David Clark. Chromatin Structure of a Transcriptionally Active Metallothionein Gene Purified from yeast Cells, Keystone Symposia - Chromatin Structure and Function. Durango, CO, 2000, pp.72.

Laboratory of Molecular Biology - Research

Ongoing research in our laboratory continues to focus on understanding the mechanism of gene expression, with the emphasis on the roles of transcriptional coactivators in gene activation. We focus on the regulation of metabolic signals triggered by changes in lipid metabolism or the regulation of heavy metal metabolism and their interaction with major cellular signal transduction pathways and transcriptional networks in the cell. Other projects in Dr. Shen’s laboratory include the transcriptional regulation of autism-associated genes, neuroligin knock-down animal model and autism disorder, and the effect of serotonin 5-HT1A receptor in feeding behavior.

One of our most recent works has focused on the mechanism of INO1 expression. In the absence of inositol, INO1 expression is induced. It has been shown that Gcn5p and Esa1p are involved in this induction by acetylating histones H3 and H4, respectively, at the INO1 promoter. The recruitment of the Gcn5p-SAGA complex to this region is a response to histone H3 Ser10 phosphorylation. This histone modification is catalyzed by the Snf1 kinase, which is recruited by Ino2p. The recruitment of histone acetylases is independent of the presence of chromatin remodelers. Chromatin remodelers provide a different avenue for INO1 activation. Several lines of evidence have shown that both Snf2p and Ino80p are required for INO1 activation. Our recent studies showed that Snf2p and Ino80p positively regulate INO1 expression by creating a more accessible nucleosomal DNA and are both required for INO1 chromatin reconfiguration and gene activation. We also showed that the Ino2p activator is essential for recruiting Ino80p and Snf2p. Furthermore, they are recruited to INO1 promoter in a sequential manner in which INO80 is required to recruit SWI/SNF. Both remodelers depart from the promoter after induction.

Although the recruitment of remodelers has been studied to some extent, both the functional role of histone acetylases and deacetylases in INO1 induction, and the recruitment and dissociation mechanism of chromatin remodelers is still not clear. Recent studies suggest that chromatin remodelers depart from the promoter region once transcription is commenced, and the action of departure might result from remodeler acetylation. Meanwhile, remodelers might then need to be deacetylated before they can be recruited to promoter. In light of these recent findings and our work, we propose a model to describe how coactivators act on INO1 chromatin during gene activation. Under repressing conditions, Opi1p, Ino2p/Ino4p and the Ume6p-Sin3p-Rpd3p complexes are present at the promoter. The histone tails of the promoter nucleosome are deacetylated by the Ume6p-Sin3p- Rpd3p complex, a corepressor- deacetylase complex. Meanwhile, activator-dependent Ino80p and Snf2p are recruited to the promoter in their acetylated form. Although the transcriptional activator and chromatin remodelers are present at the promoter under repressing conditions, the transcriptional activator is quiescent in the presence of Opi1p. This is because Opi1p mediates repression via the binding of its activator interaction domain to the repressor interaction domain of Ino2p. The remodelers remain inactive and the chromatin is in a static state.

Under inducing conditions, both Ino80p and Snf2p are deacetylated by Rpd3p followed by the dissociation of the Ume6p-Sin3p-Rpd3p complex and Opi1p from the promoter. Subsequently, the Ino2p/Ino4p activator becomes functional and Snf1p, Gcn5p and Esa1p are recruited to the promoter via Ino2p. The histone tails become acetylated. Meanwhile, the activity of SWI/SNF and INO80 is stimulated by the functional Ino2p/Ino4p, resulting in the targeted movement of promoter nucleosomes. As a result, chromatin remodeling occurs at the promoter region. Once the movement has commenced, Ino80p and Snf2p are no longer needed. More Gcn5p is recruited so both remodelers can be acetylated for departure from INO1 promoter. The dynamic nucleosomal flux allows RNA polymerase II access to its binding site and transcription is initiated. It is possible that the remaining SWI/SNF is responsible for moving promoter nucleosomes back to their original positions when the system returns to repressing conditions. As such, this model demonstrates the functional roles of acetylases and deacetylases during activation, and addresses how the remodelers dissociate from the promoter after induction. However, the details of the connections between acetylases/deacetylases and remodelers, and the impact of the remodeler’s acetylation in gene activation still need to be determined. Therefore, our current research aims to understand the mechanism of transcriptional activation by pursuing two specific aims: (1) to examine the mechanism of Ino80p acetylation and to identify which amino acid residue is responsible for Ino80p acetylation; (2) to investigate the functional roles of Ino80p acetylation in INO1 induction. These studies will provide the functional meaning and connections between chromatin remodelers and histone modifying enzymes, and yield new insight into the mechanism of gene expression.