Tae Hoon Kim PhD

Associate Professor of Genetics; Member, Yale Cancer Center; Member, Yale Stem Cell Center

Research Interests

Transcription Regulation; Transcription Elongation; Transcription Insulation; Functional Genomics; Cancer Genomics; 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

We have two broad interests in transcription: transcription insulation and transcription elongation.

Transcription Insulation

We study nuclear processes and mechanisms that segregate, fold and unfold chromosome fibers and disease causing changes that disrupt normal location, arrangement and interpretation of the human genome. Recently, we have determined the locations of a large number of insulators in the genome of primary fibroblasts. Insulators are an important class of transcriptional regulatory elements that affect gene expression by preventing the spread of heterochromatin and restricting how enhancers select their target promoters. We currently investigate the mechanisms involved in establishment and segregation of euchromatin and heterochromatin, and in folding of chromatin into higher order structures and how these insulation mechanisms are perturbed in cancer cells. We employ ChIP-seq (chromatin immunoprecipitation), 3C (chromosome conformation capture), GRO-seq (nascent RNA maping) and other functional genomics tools to define and analyze how the human genome is regulated. We utilize human cell lines and tissues (embryonic stem cells, primary fibroblasts, cancer/immortalized cells and primary cancer tissues). We couple these genome-wide experimental strategies with computational methods to systematically determine patterns, modes and mechanisms of genome expression.

Transcription Elongation

Emerging functional genomic data suggest that transcription elongation is a critical step of oncogene expression in cancers. We are interested in defining pathways and networks that are critical for elongation step of oncogene transcription. We integrate global run-on sequencing (GRO-seq), copy number analysis, functional genomics and small molecule screening to achieve a comprehensive, systems level understanding of the transcription elongation control network at oncogenes and to develop strategies for selective inhibition of the network for cancer therapy.

In parallel to these areas of investigation, we pursue development of novel functional genomic techniques and approaches for our research.

Selected Publications

  • Lark Kyun Kim, Enric Esplugues, Cornelia E. Zorca, Fabio Parisi, Yuval Kluger, Tae Hoon Kim, Niels J. Galjart, and Richard A. Flavell. Oct-1 regulates IL-17 expression by directing interchromosomal associations in conjunction with CTCF in T cells. Molecular Cell 54:56-66 (2014).
  • 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 32: 2828-2835 (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


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