Tae Hoon Kim PhD
Assistant Professor of Genetics; Member, Yale Cancer Center; Member, Yale Stem Cell Center
Research Interests
Transcriptional Regulatory Elements and Chromatin Structure; Expression of the Cancer Genome; Epigenomics
Current Projects
Our current research efforts span the following areas of investigation:- systems biology of long range transcriptional regulation - genome-wide analysis of insulator function; analysis of chromosome topology and function
- functional genomics technology development - methods for investigating transcription rate and mRNA intermediates across the human genome
- cancer epigenome - structural alterations and epigenetic perturbations
Research Summary
The human genome is predominantly composed of non-protein coding sequences (>98%) whose function remains largely undefined. A significant portion of the non-coding DNA is believed to serve as transcriptional regulatory elements that control how and when the coding fraction of the genome is used by a cell. Precise expression of each gene during development is achieved by a coordinated action of multiple transcriptional regulatory elements. In order to reconstruct and understand genome expression, we systematically identify these elements and determine how they are connected and controlled. We also investigate how aberrant use of and alterations of these elements can cause cancers. Our laboratory combines traditional molecular and biochemical methods with bioinformatics and high-throughput functional genomics techniques to analyze these elements.
Extensive Research Description
Chromatin domains and insulator function in cancers.
Insulators represent a unique class of regulatory elements that serves
to segregate distinct genomic regions. Since insulators maintain proper
genomic and chromatin domains, these elements represent a novel class
of tumor suppressors. Recently, we reported a large number of
insulators in the human genome and described their genomic distribution, sequence determinant of binding and mode of their evolutionary change. We are defining distinct functional
classes of insulators and determining molecular mechanisms of their action.
Functional Genomics.
We develop new methods and strategies for identifying and characterizing other
regulatory elements and for analyzing mechanisms of genome expression. We employ various technologies that are available:
high throughput sequencing, custom DNA microarrays, and various genomic
libraries.
Selected Publications
- Yoon Jung Kim*, Celeste Greer*, Katharine Cecchini, Lyndsay N. Harris, David P. Tuck and Tae Hoon Kim. HDAC inhibitors induce transcriptional repression of high copy number genes in breast cancer through elongation blockade. Oncogene advance online publication 25 February 2013. *These authors contributed equally.
- Tae Hoon Kim* and Job Dekker*. Crosslinking Technologies for Analysis of Chromatin Structure and Function. in Molecular Cloning: A Laboratory Manual (ed. M. R. Green and J. Sambrook). Cold Spring Harbor Laboratory Press, Cold Spring Harbor (2012). *corresponding authors
- Bora E. Baysal, Sharen E. McKay, Yoon Jung Kim, Zimei Zhang, Linda Alila, Joan E. Willett-Brozick, Karel Pacak, Tae Hoon Kim and Gerald S. Shadel. Genomic imprinting at a boundary element flanking the SDHD locus. Human Molecular Genetics 20:4452-61 (2011).
- Yoon Jung Kim, Katharine R. Cecchini and Tae Hoon Kim. Conserved, developmentally regulated mechanism couples chromosomal looping and heterochromatin barrier activity at the homeobox gene A locus. Proceedings of National Academy of Sciences, USA 108:7391-7396 (2011).
- David A. Wacker, Yoon Jung Kim and Tae Hoon Kim. Chromatin modifications distinguish genomic features and physical organization of the nucleus. in Handbook of Epigenetics: The New Molecular and Medical Genetics (ed. T. Tollefsbol). Elsevier Academic Press (2010).
- Kerrigan B. Gilbert, Tae Hoon Kim, Rashmi Gupta, E. Peter Greenberg and Martin Schuster. Global position analysis of the Pseudomonas aeruginosa quorum-sensing transcription factor LasR. Molecular Microbiology 73:1072-1085 (2009).
- Katharine R. Cecchini, A. Raja Banerjee and Tae Hoon Kim. Toward a genome-wide reconstruction of cis-regulatory networks in the human genome. Seminars in Cell and Developmental Biology (2009).
- David A. Wacker and Tae Hoon Kim. From sextant to GPS: twenty-five years of mapping the genome with ChIP. Journal of Cellular Biochemistry 107:6-10 (2009).
- Tae Hoon Kim*, Leah O. Barrera and Bing Ren. ChIP-chip for genome-wide analysis of protein binding in mammalian cells. Current Protocols in Molecular Biology 79 Unit 21.13 (2007). *corresponding author
- The ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799-816 (2007).
Selected Publications
- Yoon Jung Kim*, Celeste Greer*, Katharine Cecchini, Lyndsay N. Harris, David P. Tuck and Tae Hoon Kim. HDAC inhibitors induce transcriptional repression of high copy number genes in breast cancer through elongation blockade. Oncogene advance online publication 25 February 2013. *These authors contributed equally.
- Tae Hoon Kim* and Job Dekker*. Crosslinking Technologies for Analysis of Chromatin Structure and Function. in Molecular Cloning: A Laboratory Manual (ed. M. R. Green and J. Sambrook). Cold Spring Harbor Laboratory Press, Cold Spring Harbor (2012). *corresponding authors
- Bora E. Baysal, Sharen E. McKay, Yoon Jung Kim, Zimei Zhang, Linda Alila, Joan E. Willett-Brozick, Karel Pacak, Tae Hoon Kim and Gerald S. Shadel. Genomic imprinting at a boundary element flanking the SDHD locus. Human Molecular Genetics 20:4452-61 (2011).
- Yoon Jung Kim, Katharine R. Cecchini and Tae Hoon Kim. Conserved, developmentally regulated mechanism couples chromosomal looping and heterochromatin barrier activity at the homeobox gene A locus. Proceedings of National Academy of Sciences, USA 108:7391-7396 (2011).
- David A. Wacker, Yoon Jung Kim and Tae Hoon Kim. Chromatin modifications distinguish genomic features and physical organization of the nucleus. in Handbook of Epigenetics: The New Molecular and Medical Genetics (ed. T. Tollefsbol). Elsevier Academic Press (2010).
- Kerrigan B. Gilbert, Tae Hoon Kim, Rashmi Gupta, E. Peter Greenberg and Martin Schuster. Global position analysis of the Pseudomonas aeruginosa quorum-sensing transcription factor LasR. Molecular Microbiology 73:1072-1085 (2009).
- Katharine R. Cecchini, A. Raja Banerjee and Tae Hoon Kim. Toward a genome-wide reconstruction of cis-regulatory networks in the human genome. Seminars in Cell and Developmental Biology (2009).
- David A. Wacker and Tae Hoon Kim. From sextant to GPS: twenty-five years of mapping the genome with ChIP. Journal of Cellular Biochemistry 107:6-10 (2009).
- Tae Hoon Kim*, Leah O. Barrera and Bing Ren. ChIP-chip for genome-wide analysis of protein binding in mammalian cells. Current Protocols in Molecular Biology 79 Unit 21.13 (2007). *corresponding author
- The ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799-816 (2007).
- Tae Hoon Kim*, Ziedulla K. Abdullaev, Andrew D. Smith, Keith A. Ching, Dmitri I. Loukinov, Roland D. Green, Michael Q. Zhang, Victor V. Lobanenkov and Bing Ren*. Analysis of the vertebrate insulator protein CTCF binding sites in the human genome. Cell 128:1231-1245 (2007). *corresponding authors
- Tae Hoon Kim* and Bing Ren*. Genome-wide Analysis of Protein-DNA Interactions. Annual Review of Genomics and Human Genetics 7:81-102 (2006). *corresponding authors
- Tae Hoon Kim, Leah O. Barrera, Ming Zheng, Chunxu Qu, Michael A. Singer, Todd A. Richmond, Yingnian Wu, Roland D. Green and Bing Ren. A high-resolution map of active promoters in the human genome. Nature 436:876-880 (2005).
