Emily Wiley

Professor of Biology

Email: ewiley@kecksci.claremont.edu
Office: Keck Science Center 210
Phone: 909-607-9698
Office Hours:
Web Site: https://sites.google.com/site/wileylabs/Home

Educational Background

Postdoc, University of Rochester; Fred Hutchinson Cancer Research Center
Ph.D., University of Washington
B.A., Western Washington University

Courses Taught

• Molecular Biology (Bio170L)
• Molecular Seminar (Bio173L)
• Accelerated Integrated Science Sequence (AISS)
• Introductory Biological Chemistry (IBC) (Bio40)
• Drugs and Molecular Medicine (Bio144)
• Biochemistry (Bio177)
• Introductory Biology (cell/molecular/genetics/physiology) and Introductory Laboratory (Bio43L)
• Genetic Engineering and Biotechnology (Bio84L)

Research Interests

My lab studies the relationships between histone modifications, chromatin structure, the control of gene expression, and nuclear differentiation using the protozoan Tetrahymena thermophila as a model system. Most of our work focuses on exploring the role of histone deacetylases in chromatin dynamics and heterochromatin assembly, and histone clipping mechanisms. EXTERNAL GRANTS: 2014-18 NSF Improving Undergraduate Science Education (IUSE) Award: “The Ciliate Genomics Consortium Model for Sustainable Teaching-Research Integration” 2012-17 NSF Sub-Award: “Genomics of Tetrahymena” 2006-13 NSF CAREER Award: “Investigating Chromatin Assembly Pathways Through Histone Deacetylases”

Thesis Topics

• Cellular localization of histone deacetylase enzymes through GFP-tagging;
• Engineering gene knockout constructs of chromatin modification enzymes, generation of knockout cell lines, and phenotype characterization of mutant cells;
• Identification of protein complexes that modify chromatin;
• Mechanistic roles for histone deacetylase enzymes in the control of gene expression and other cellular processes

Selected Publications

1. Wiley, E.A. and Chalker, D. (2016). A community model for course-based student research that advances faculty scholarship. CUR Quarterly 37(2).
   Article – URL not found
2. Yale, K., Neuman, M., Bulley, E., Tackett, A., Chait, B.T., Wiley, E.A. (2016). Phosphorylation-dependent targeting of Tetrahymena HP1 to condensed chromatin. mSphere 4  4.
   [Article – URL not found]
3. Wiley, E.A. and Stover, N. (2014). Immediate dissemination of student discoveries to a model organism database enhances classroom-based research experiences. CBE Life Sci. Educ 13(1): 131-8.
4. Smith, J.J., Wiley, E.A., Cassidy-Hanley, D. (2012). Tetrahymena in the Classroom. Methods in Cell Biology 109: 411-30.
5. Slade, KM., Freggiaro, S., Cottrell, K.A., Smith, J.J., and Wiley, E.A. (2011). Sirtuin-mediated nuclear differentiation and programmed degradation in Tetrahymena. BMC Cell Biology 12(1):40-54  12(1): 40-54.
6. Sean R. Gallagher and Emily A. Wiley. (2008). Current Protocols: Essential Laboratory Techniques. (Gallagher, S.R. and Wiley, E.A, eds.) Wiley and Sons, Inc., New Jersey.
7. Coyne, R.S., Thiagarajan, M., Jones, K.M., Wortman, J.R., Tallon, L.J., Haas, B.J., Cassidy-Hanley, D.M., Wiley, E.A., et al. (2008). Refined annotation and assembly of the Tetrahymena thermophila genome sequence through EST analysis, comparative genomic hybridization, and targeted gap closure. BMC Genomics 9: 562-579.
8. Smith, J., Torigoe, S., Maxson, J., Fish, L., and Wiley, E.A. (2008). A class II HDAC deacetylates newly-synthesized histones in Tetrahymena. Eukaryotic Cell  7(3): 471-482.
9. Parker, K., Maxson, J., Mooney, A., and Wiley, E.A. (2007). Class I histone deacetylase Thd1p promotes global chromatin condensation in Tetrahymena thermophila. Eukaryotic Cell 6: 1913-1924.
10. Wiley, E.A., Myers, T., Parker, K., Braun, T., Yao, M.-C . (2005). The class I histone deacetylase Thd1p affects nuclear integrity in Tetrahymena thermophila. Eukaryotic Cell 4: 981-990.
    Abstract – Class I histone deacetylases (HDACs) participate in the regulation of DNA-templated processes such as transcription and replication. Members of this class can act locally at specific sites, or they can act more globally, contributing to a baseline acetylation state, both of which actions may be important for genome maintenance and organization. We previously identified a macronuclear-specific class I HDAC in Tetrahymena thermophila called Thd1p, which is expressed early in the development of the macronucleus when it initially becomes transcriptionally active. To test the idea that Thd1p is important for global chromatin integrity in an active macronucleus, Tetrahymena cells reduced in expression of Thd1p were generated. We observed phenotypes that indicated loss of chromatin integrity in the mutant cells, including DNA fragmentation and extrusion of chromatin from the macronucleus, variable macronuclear size and shape, enlarged nucleoli, and reduced phosphorylation of histone H1 from bulk chromatin. Macronuclei in mutant cells also contained more DNA. This observation suggests a role for Thd1p in the control of nuclear DNA content, a previously undescribed role for class I HDACs. Together, these phenotypes implicate Thd1p in the maintenance of macronuclear integrity in multiple ways, probably through site-specific changes in histone acetylation since no change in the acetylation levels of bulk histones was detected in mutant cells.
11. Wiley, E.A., Mizzen, C., Allis, C.D. (2000). Isolation and characterization of in vivo modified histones and an activity gel assay for identification of histone acetyltransferases. Methods in Cell Biology: Tetrahymena thermophila. (James Forney and David Asai, eds.) Academic Press 62: 379-394.
12. Wiley, E.A., Ohba, R., Yao, M.-C., Allis, C.D. (2000). Developmentally regulated Rpd3p homolog specific to the transcriptionally active macronucleus of vegetative Tetrahymena thermophila. Molecular and Cellular Biology  23: 8319-8328.
    Abstract – A clear relationship exists between histone acetylation and transcriptional output, the balance of which is conferred by opposing histone acetyltransferases (HATs) and histone deacetylases (HDACs). To explore the role of HDAC activity in determining the transcriptional competency of chromatin, we have exploited the biological features of Tetrahymena as a model. Each vegetative cell contains two nuclei: a somatic, transcriptionally active macronucleus containing hyperacetylated chromatin and a transcriptionally silent, germ line micronucleus containing hypoacetylated histones. Using a PCR-based strategy, a deacetylase gene (named THD1) encoding a homolog of the yeast HDAC Rpd3p was cloned. Thd1p deacetylates all four core histones in vitro. It resides exclusively in the macronucleus during vegetative growth and is asymmetrically distributed to developing new macronuclei early in their differentiation during the sexual pathway. Together, these data are most consistent with a potential role for Thd1p in transcriptional regulation and suggest that histone deacetylation may be important for the differentiation of micronuclei into macronuclei during development.
13. Huang, H., Smothers, J.F., Wiley, E.A., Allis, C.D. (1999). A nonessential HP1-like protein affects starvation-induced assembly of condensed chromatin and gene expression in macronuclei of Tetrahymena thermophila. Molecular and Cellular Biology 19: 3624-3634.
    Abstract – Heterochromatin represents a specialized chromatin environment vital to both the repression and expression of certain eukaryotic genes. One of the best-studied heterochromatin-associated proteins is Drosophila HP1. In this report, we have disrupted all somatic copies of the Tetrahymena HHP1 gene, which encodes an HP1-like protein, Hhp1p, in macronuclei (H. Huang, E. A. Wiley, R. C. Lending, and C. D. Allis, Proc. Natl. Acad. Sci. USA 95:13624-13629, 1998). Unlike the Drosophila HP1 gene, HHP1 is not essential in Tetrahymena spp., and during vegetative growth no clear phenotype is observed in cells lacking Hhp1p (DeltaHHP1). However, during a shift to nongrowth conditions, the survival rate of DeltaHHP1 cells is reduced compared to that of wild-type cells. Upon starvation, Hhp1p becomes hyperphosphorylated concomitant with a reduction in macronuclear volume and an increase in the size of electron-dense chromatin bodies; neither of these morphological changes occurs in the absence of Hhp1p. Activation of two starvation-induced genes (ngoA and CyP) is significantly reduced in DeltaHHP1 cells while, in contrast, the expression of several growth-related or constitutively expressed genes is comparable to that in wild-type cells. These results suggest that Hhp1p functions in the establishment and/or maintenance of a specialized condensed chromatin environment that facilitates the expression of certain genes linked to a starvation-induced response.
14. Huang, H., Wiley, E.A., Lending, C.R., Allis, C.D. (1998). An HP1-like protein is missing from transcriptionally silent micronuclei of Tetrahymena. Proceedings of the National Academy of Science 95: 13624-13629.
    Abstract – We report the identification and cloning of a 28-kDa polypeptide (p28) in Tetrahymena macronuclei that shares several features with the well studied heterochromatin-associated protein HP1 from Drosophila. Notably, like HP1, p28 contains both a chromodomain and a chromoshadow domain. p28 also shares features with linker histone H1, and like H1, p28 is multiply phosphorylated, at least in part, by a proline-directed, Cdc2-type kinase. As such, p28 is referred to as Hhp1p (for H1/HP1-like protein). Hhp1p is missing from transcriptionally silent micronuclei but is enriched in heterochromatin-like chromatin bodies that presumably comprise repressed chromatin in macronuclei. These findings shed light on the evolutionary conserved nature of heterochromatin in organisms ranging from ciliates to humans and provide further evidence that HP1-like proteins are not exclusively associated with permanently silent chromosomal domains. Our data support a view that members of this family also associate with repressed states of euchromatin.