Kim, Tae Hoon

Permanent URI for this collectionhttps://hdl.handle.net/10735.1/4378

Tae Hoon Kim serves as an Associate Professor of Biological Sciences. His research focuses on the mechanisms of human genome expression involving transcription insulation, transcription elongation, and long range chromosomal interactions. He is also the founder and head of UTD's Functional Genomics Laboratory.

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    Long Genes Linked to Autism Spectrum Disorders Harbor Broad Enhancer-Like Chromatin Domains
    (Cold Spring Harbor Laboratory Press) Zhao, Y. -T; Kwon, D. Y.; Johnson, B. S.; Fasolino, M.; Lamonica, J. M.; Kim, Yoon Jung; Zhao, B. S.; He, C.; Vahedi, G.; Kim, Tae Hoon; Zhou, Z.; Kim, Yoon Jung; Kim, Tae Hoon
    Genetic variants associated with autism spectrum disorders (ASDs) are enriched in genes encoding synaptic proteins and chromatin regulators. Although the role of synaptic proteins in ASDs is widely studied, the mechanism by which chromatin regulators contribute to ASD risk remains poorly understood. Upon profiling and analyzing the transcriptional and epigenomic features of genes expressed in the cortex, we uncovered a unique set of long genes that contain broad enhancer-like chromatin domains (BELDs) spanning across their entire gene bodies. Analyses of these BELD genes show that they are highly transcribed with frequent RNA polymerase II (Pol II) initiation and low Pol II pausing, and they exhibit frequent chromatin-chromatin interactions within their gene bodies. These BELD features are conserved from rodents to humans, are enriched in genes involved in synaptic function, and appear post-natally concomitant with synapse development. Importantly, we find that BELD genes are highly implicated in neurodevelopmental disorders, particularly ASDs, and that their expression is preferentially down-regulated in individuals with idiopathic autism. Finally, we find that the transcription of BELD genes is particularly sensitive to alternations in ASD-associated chromatin regulators. These findings suggest that the epigenomic regulation of BELD genes is important for post-natal cortical development and lend support to a model by which mutations in chromatin regulators causally contribute to ASDs by preferentially impairing BELD gene transcription.
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    Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions
    (Public Library of Science, 2015-08-24) Nwigwe, I. J.; Kim, Yoon Jung; Wacker, D. A.; Kim, Tae Hoon; Chadwick, B. P.; Kim, Yoon Jung; Kim, Tae Hoon
    CCCTC binding factor (CTCF) is involved in organizing chromosomes into mega base-sized, topologically associated domains (TADs) along with other factors that define sub-TAD organization. CTCF-Cohesin interactions have been shown to be critical for transcription insulation activity as it stabilizes long-range interactions to promote proper gene expression. Previous studies suggest that heterochromatin boundary activity of CTCF may be independent of Cohesin, and there may be additional mechanisms for defining topological domains. Here, we show that a boundary site we previously identified known as CTCF binding site 5 (CBS5) from the homeotic gene cluster A (HOXA) locus exhibits robust promoter activity. This promoter activity from the CBS5 boundary element generates a long noncoding RNA that we designate as boundary associated long noncoding RNA-1 (blncRNA1). Functional characterization of this RNA suggests that the transcript stabilizes long-range interactions at the HOXA locus and promotes proper expression of HOXA genes. Additionally, our functional analysis also shows that this RNA is not needed in the stabilization of CTCF-Cohesin interactions however CTCF-Cohesin interactions are critical in the transcription of blncRNA1. Thus, the CTCF-associated boundary element, CBS5, employs both Cohesin and noncoding RNA to establish and maintain topologically associated domains at the HOXA locus.
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    A Novel Virus-Inducible Enhancer of the Interferon-β Gene with Tightly Linked Promoter and Enhancer Activities
    (2014-10-27) Banerjee, A. Raja; Kim, Yoon Jung; Kim, Tae Hoon; Kim, Yoon Jung; Kim, Tae Hoon
    Long-range enhancers of transcription are a key component of the genomic regulatory architecture. Recent studies have identified bi-directionally transcribed RNAs emanating from these enhancers known as eRNAs. However, it remains unclear how tightly coupled eRNA production is with enhancer activity. Through our systematic search for long-range elements that interact with the interferon-beta gene, a model system for studying inducible transcription, we have identified a novel enhancer, which we have named L2 that regulates the expression of interferon-beta. We have demonstrated its virus-inducible enhancer activity by analyzing epigenomic profiles, transcription factor association, nascent RNA production and activity in reporter assays. This enhancer exhibits intimately linked virus-inducible enhancer and bidirectional promoter activity that is largely dependent on a conserved Interferon Stimulated Response Element and robustly generates virus inducible eRNAs. Notably, its enhancer and promoter activities are fully retained in reporter assays even upon a complete elimination of its associated eRNA sequences. Finally, we show that L2 regulates IFNB1 expression by siRNA knockdown of eRNAs, and the deletion of L2 in a BAC transfection assay. Thus, L2 is a novel enhancer that regulates IFNB1 and whose eRNAs exert significant activity in vivo that is distinct from those activities recapitulated in the luciferase reporter assays.

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