11:10-12:00, Rm 103

Genetics and genomics, epigeneticsN-18-13Analysis of the common mitochondrial DNA deletion of humanlymphocyte by ionizing radiationEun Ju Kim, Sun Young Kim, Hyun Jin Yun, Chun-Ho Kim and Chang-Mo KangLaboratory of Cytogenetics and Tissue Regeneration, Korea Institute of Radiological & MedicalSciences, Seoul 139-706, KoreaWe examined whether radiation induces the 4977-base pair (bp) deletion in mitochondrialDNA (mtDNA) recovered from human blood. Human blood DNA was amplified andquantified by real-time polymerase chain reaction (PCR) using primer sets for total andmutant mtDNA, plus probes labeled with the fluorescent dyes hexachloro-6-carboxyfluorescein (Hex) and 6-carboxyfluorescein (FAM). The first-round PCRgenerated multiple products, including true deletions and artifacts, which were thenrecovered and used as the template for a second-round of PCR. Putative mtDNAdeletions could only be confirmed if they were recovered by the first-round of PCR. Theobtained estimates of mtDNA ‘common deletion’(CD) levels were remarkably close tothe theoretical values (correlation coefficient = 3.2). Thus, we herein describe a multiplexreal-time PCR assay capable of quantifying mtDNA bearing the CD in human blood froman individual diagnosed with radiation exposure and radiation-induced injury.N-18-16A new molecular bridge between RelA/p65 and chromatin remodelingof NF-κB target gene promoters via histone acetyltransferase TIP60Jung-Woong Kim, Sang-Min Jang, Chul-hong Kim, Joo-Hee An, Eun-Jin Kang,Kyung-Hee ChoiDepartment of Life Science (BK21 program), College of Natural Sciences, Chung-Ang University,221, Heuksuk-Dong, Dongjak-Ku, Seoul 156-756, KoreaThe nuclear factor-kappaB (NF-κB) family of transcription factors is involved in theexpressions of numerous genes involved in processes such as development, apoptosis,inflammatory responses and oncogenesis. Here, we identified four NF-κB target genesthat are tightly modulated by TIP60. We found that TIP60 interacts with the NF-κBRelA/p65 subunit and increases its transcriptional activity. Although TIP60 binds withRelA/p65 using its histone acetyltransferase domain, TIP60 does not directly acetylateRelA/p65. However, TIP60 maintained acetylated K310 RelA/p65 levels in the TNF-αdependent NF-κB signaling pathway. In a ChIP assay, TIP60 was primarily recruited tothe IL-6, IL-8, C-IAP1 and XIAP promoters in a TNF-αstimulation, followed by acetylationof histones H3 and H4. Chromatin remodeling by TIP60 involved the sequentialrecruitment of acetyl-K310 RelA/p65 to its target gene promoter regions. Furthermore, weshowed that up-regulated TIP60 expression was significantly correlated with acetyl-K310RelA/p65 expressions in hepatocarcinoma tissues. Taken together, these results suggestthat TIP60 is involved in the NF-κB pathway through a protein interaction with RelA/p65and that it modulates the transcriptional activity of RelA/p65 in NF-κB dependent geneexpression.N-18-14Menin as a Tumor Suppressor mediates Histone H3 Lysine9MethylationJihyeon Lim, Yong-Jin Yang, Ye-hyang Kim and Eun-Jung ChoDepartment of Pharmacy, Sungkyunkwan University, Suwon 440-776, KoreaMenin is a tumor suppressor protein mutated in patients with inherited tumor syndromemultiple endocrine neoplasia type 1 (MEN1), which is characterized by parathyroidhyperplasia and tumors of the pituitary and pancreatic isles. Men1 patients typicallyinherit loss of function mutations in the MEN1 gene which encodes menin, and tumorsarise following loss of the remaining wild-type allele. Conditional MEN1 knocked out micealso develop a similar phenotype, implying that menin has a role in endocrine tissuehomeostasis and tumor suppression. However, the molecular mechanism for menininducedsuppression of MEN1 tumorigenesis remains unclear. Menin has been shown tointeract with and modulate the activity of histone methyltransferases such as mixedlineage leukemia proteins, the SET-1 domain-containing histone 3 lysine 4 (H3K4)methyltransferases, to up-regulate the expression of certain cyclin-dependent kinaseinhibitors and homeobox (Hox) gene. Here, we show that menin also has an ability tointeract with other kind of histone methyltransferase to down-regulate transcription. Wepropose that menin serves as a chromatin remodelling mediator by recruiting either activeor repressive histone modifiers and this property might be the basis for endocrine tumorsuppression by menin.N-18-17A Potential Role of Upstream Signaling for the Regulation of TumorSuppressor MeninYu-Na Kim and Eun-Jung ChoCollege of Pharmacy, Sungkyunkwan University, Suwon 446-746, KoreaMenin, encoded by the multiple endocrine neoplasia type 1(MEN1) gene, is a tumorsuppressor and functions as a transcriptional regulator. Menin acts as a transcriptionfactor by tethering chromatin remodeling activities. For example, it up-regulates certaincyclin-dependent kinase inhibitors p18Ink4c and p27Kip1 through interacting withMLL1/MLL2 protein complexes which have histone H3 lysine 4 methyltransferase (HMT)activities. Menin also represses transcription by counteracting the activity of JunD in ahistone deacetylase (HDAC)-dependent manner. To understand how menin can affecttranscription either positively or negatively, we have searched upstream regulatorysignals that target menin to allow chromatin remodeling and gene regulation. We havesearched an upstream regulatory mechanism that targets menin to exert chromatinremodeling and gene regulation. In this effort, we found that the interaction of menin andHDAC1 was affected by GSK3β. The GSK3 inhibitor IX and SB216763 reduced theinteraction of menin with HDAC1, whereas it showed no effect on that with either MLL2 orSuv39H1. Our data show that activity of menin on chromatin remodeling and transcriptionregulation can be possibly regulated by GSK.N-18-15Histone chaperones cooperate to mediate Mef2-targeted transcriptionalregulation during skeletal myogenesisJae-Hyun Yang¹, Ji-Hyun Choi¹, Hyonchol Jang², Jin Young Park¹, Hong-DukYoun², Eun-Jung Cho¹¹School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Korea,²Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, KoreaHistone chaperones function in histone transfer and regulate the nucleosome occupancyand the activity of genes. HIRA is a replication-independent (RI) histone chaperone that islinked to transcription and various developmental processes. Here, we show that HIRAinteracts with Mef2 and contributes to the activation of Mef2-target genes during muscledifferentiation. Asf1 cooperated with HIRA and was indispensable for Mef2-dependenttranscription. The HIRA R460A mutant, which is defective in Asf1 binding, lost thetranscriptional co-activation. In addition, the role of Cabin1, previously reported as a Mef2repressor and as one of the components of the HIRA-containing complex, was delineatedin Mef2/HIRA-mediated transcription. Cabin1 associated with the C-terminus of HIRA viaits N-terminal domain and suppressed Mef2/HIRA-mediated transcription. Expression ofCabin1 was dramatically reduced upon myoblast differentiation, which may allow Mef2and HIRA/Asf1 to resume their transcriptional activity. HIRA led to more permeablechromatin structure marked by active histone modifications around the myogeninpromoter. Our results suggest that histone chaperone complex components contribute tothe regulation of Mef2 target genes for muscle differentiation.N-18-18The fs-THz radiation in mouse skin induces genetic change in early andlate phasesKyu-Tae Kim¹, Ae-Kyung Park¹, Jong-Hyuk Lee¹, Oh-Sang Kwon², Seong-Jin Jo²,Sun-Young Yoon², Jae-Hun Park³, Seong-Hoon Jeong³, Dae-Hoon Han³, Gun-SikPark⁴and Woong-Yang Park¹¹Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, ²Department of Dermatology, Seoul National University Hospital, Seoul 110-744, ³fs-THzLaboratory, Support Building, Pohang Accelerator Laboratory, Pohang 790-784, ⁴Center for THz-Bio Application Systems and Department of Physics and Astronomy, Seoul National University,Seoul 151-742, KoreaTerahertz region has been blazing a trail in the electromagnetic field with a prerequisitecondition of validation for bio-safety before practical use in a variety of areas involvingTHz-Sensing, THz-Photonics and THz-Electronics. Here we show in vivo approach tostudy genetic effect of THz-radiation (100~1000 um, 0.254 nJ/pulse, 185 fs) on the hairclippedmidback, targeted in 1cm diameter, of anesthetized mice (C57BL/6, male,8weeks). 2 parameters tracing early-(sampling 1 hour after 1 hour radiation) and lateresponsive(sampling 24 hours after 1 hour radiation) change of the gene expression inskin, spleen and liver are set, and each parameter has 2 groups with THz-radiated andcontrol. In case of skin tissue, un-exposed part is additionally used as a negative controlto compare each other without individual variation. Quantitative RT-PCR is performed inensuing RNA isolation initially with inflammatory related genes including PPARa andCOX-2. Both in early and late phase PPARa and COX-2 is elevated in skin tissue underthe radiated condition compared to un-exposed part and control group as well. Distinctpoint between early- and late phase is the expression pattern of p21; the former showsup-regulation, while it is dramatically decreased at the latter.298 Korean Society for Biochemistry and Molecular Biology