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Epithelial Epigenetics and Development

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Chin Yan Lim

Chin Yan Lim obtained her Ph.D. from the University of California, San Diego in 2006, as a recipient of the A*STAR National Science Scholarships. Her thesis on the characterization of core promoter elements in transcriptional was carried out under the supervision of Dr. James T. Kadonaga.

Upon completing a postdoctoral fellowship with Dr. Bing Lim at the Genome Institute of Singapore where she analyzed critical transcriptional networks controlling embryonic stem cell pluripotency, she joined the laboratory of Drs. Davor Solter and Barbara Knowles in IMB as a senior research fellow in 2008 to pursue and develop her research interests in understanding epigenetic controls of cellular specification. In 2013, Chin was appointed as a Junior Principal Investigator in IMB, with a research focus on the role of epigenetic regulation in epidermal stem cell renewal and differentiation.

Each type of cells in our body contains unique chromatin landscapes that facilitate the expression of genes which define the cellular phenotype and function. As stem/progenitor cells differentiate, reversible modifications are made to the chromatin to allow for changes in gene expression. Therefore, understanding the epigenetic mechanisms that control the delicate balance between pluripotency and differentiation in stem cells is fundamental to our appreciation of mammalian development, and to our ability to harness this knowledge for therapeutic applications.

The lab is focused on investigating the major principles of how changes in chromatin dynamics influence cell identity specification during embryonic development. Using the developing mouse epidermis as a model, we aim to identify and functionalize novel chromatin-associated factors that regulate the proliferation and differentiation of lineage-committed stem cells.

On-going projects in the lab involve genomics approaches to delineate the chromatin landscapes of epidermal progenitor cells, and functional screens to identify transcriptional and epigenetic regulators of progenitor cell renewal and differentiation. We anticipate that the epigenetic regulatory mechanisms identified in epidermal stem cells will also provide testable insight into common principles underlying the specification and maintenance of other stem/progenitor cells of the developing embryo.

Group Members

 Research Fellow Nichola Helen Cooper
 Research Officers Shue Yan Ting

Shaktheeshwari D/O Silvaraju

James C, Zhao TY, Rahim A, Saxena P, Muthalif NA, Uemura T, Tsuneyoshi N, Ong S, Igarashi K, Lim CY, Dunn NR, Vardy LA. MINDY1 is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal. Stem Cells. 2018 Apr 12. doi: 10.1002/stem.2830 Link
Ho L, van Dijk M, Chye STJ, Messerschmidt DM, Chng SC, Ong S, Yi LK, Boussata S, Goh GH, Afink GB, Lim CY, Dunn NR, Solter D, Knowles BB, Reversade B. ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice. Science. 2017 Aug 18;357(6352):707-713. doi: 10.1126/science.aam6607 Link
Han Y, Wang F, Lim CY, Chi H, Chen D, Wang F, Jiao X. High-Performance Nano-Photoinitiators with Improved Safety for 3D Printing. ACS Appl Mater Interfaces. 2017 Sep 27;9(38):32418-32423. doi: 10.1021/acsami.7b08399 Link
Piatti P, Lim CY, Nat R, Villunger A, Geley S, Shue YT, Soratroi C, Moser M, Lusser A. Embryonic stem cell differentiation requires full length Chd1. Sci Rep. 2015 Jan 26;5:8007. doi: 10.1038/srep08007. PubMed PMID: 25620209; PubMed Central PMCID: PMC4306112. Link
Lim CY, Solter D, Knowles BB, Damjanov I. “Development of Teratocarcinomas and Teratomas in Severely Immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/Szj (NSG) Mice.” Stem Cells Dev. 2015 Jul 1;24(13):1515-20. doi: 10.1089/scd.2015.0033
Young T, Poobalan Y, Tan EK, Tao S, Ong S, Wehner P, Schwenty-Lara J, Lim CY, Sadasivam A, Lovatt M, Wang ST, Ali Y, Borchers A, Sampath K, Dunn NR. The PDZ domain protein Mcc is a novel effector of non-canonical Wnt signaling during convergence and extension in zebrafish. Development. 2014 Sep;141(18):3505-16. doi: 10.1242/dev.114033. PubMed PMID: 25183869. Link
Lim, C.Y.,# Reversade, B., Knowles, B.B., and Solter, D. (2013) Optimal histone H3 to linker histone chromatin ratio is vital for mesodermal competence in Xenopus. Development 140: 853-860 #corresponding author.
Avery S, Hirst AJ, Baker D, Lim CY, Alagaratnam S, Skotheim RI, Lothe RA, Pera MF, Colman A, Robson P, Andrews PW, Knowles BB. BCL-XL mediates the strong selective advantage of a 20q11.21 amplification commonly found in human embryonic stem cell cultures. Stem Cell Reports. 2013 Oct 31;1(5):379-86. doi: 10.1016/j.stemcr.2013.10.005. eCollection 2013. PubMed PMID: 24286026; PubMed Central PMCID: PMC3841249. Link
Goh, A.M., Lim, C.Y., Chiam, P.C., Li, L., Mann, M.B., Mann, K.M., Menendez, S., Lane, D.P. (2012) Using targeted transgenic reporter mice to study promoter-specific p53 transcriptional activity. Proc. Natl Acad. Sci. USA 109 (5): 1685-1690
Thiesen, J.W.M.*, Lim, C.Y.*, and Kadonaga, J.T. (2010) Three key subregions contribute to the function of the downstream RNA polymerase II core promoter. Mol Cell Biol 30: 3471-3479 *equal contribution.
Lorthongpanich, C., Solter, D., Lim, C.Y. (2010) Nuclear reprogramming in zygotes. Int’l J. Dev. Biol. 54 (11-12): 1631-1640
Lim, C. Y., Tam, W. L., Zhang, J., Ang, Y.S., Jia, H., Lipovich, L., Ng, H.H., Wei, C.L., Sung, W.K., Robson, P., Yang, H., and Lim, B. (2008). Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages. Cell Stem Cell 3: 543-554
Tam, W. L., Lim, C. Y., Han, J., Zhang, J., Ang, Y. S., Ng, H. H., Yang, H., and Lim, B. (2008). Tcf3 regulates embryonic stem cell pluripotency and self-renewal by the transcriptional control of multiple lineage pathways. Stem Cells 26: 2019 – 2031
Konev, A. Y., Tribus, M., Park, S. Y., Podhraski, V., Lim, C. Y., Emelyanov, A. V., Vershilova, E., Pirrotta, V., Kadonaga, J. T., Lusser, A., and Fyodorov, D. V. (2007). CHD1 motor protein is required for deposition of histone variant H3.3 into chromatin in vivo. Science 317: 1087-1090.
Lim, C. Y., Santoso, B., Boulay, T., Dong, E., Ohler, U., and Kadonaga, J. T. (2004). The MTE, a new core promoter element for transcription by RNA polymerase II. Genes Dev 18: 1606-1617.