이대엽 교수
Daeyoup Lee
KAIST 생명과학과 · 생화학·유전·분자생물학
연구실 소개
이대엽 교수의 연구실은 히스톤 수정과 전사 조절의 분자 기전을 중심으로, RNA 중합효소 II의 전사 동역학과 관련된 히스톤 에너지 조절 메커니즘을 규명하고 있습니다. 특히 히스톤 탈아세틸화, 메틸화, 인산화 등 다양한 히스톤 변형 간의 상호작용과 이들이 유전자 발현에 미치는 영향을 다각도로 연구하고 있으며, 전사 조절 복합체와 종양 suppressor 단백질(p53 등) 간의 상호작용 메커니즘을 밝혀내고 있습니다. 또한, 염기서열 기반의 대량 유전자 분석을 위한 자동화된 시퀀싱 데이터 처리 플랫폼 개발을 통해 체계적인 에피제네틱스 연구를 지원하고 있습니다.
연구 현황
연구 성과 추이
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
주요 논문
15Nucleosomes must be deacetylated behind elongating RNA polymerase II to prevent cryptic initiation of transcription within the coding region. RNA polymerase II signals for deacetylation through the methylation of histone H3 lysine 36 (H3K36), which provides the recruitment signal for the Rpd3S histone deacetylase complex (HDAC). The recognition of methyl H3K36 by Rpd3S requires the chromodomain of its Eaf3 subunit. Paradoxically, Eaf3 is also a subunit of the NuA4 acetyltransferase complex, yet
The SWI/SNF complex is required for the transcription of several genes and has been shown to alter nucleosome structure in an ATP-dependent manner. The tumor suppressor protein p53 displays growth and transformation suppression functions that are frequently lost in mutant p53 proteins detected in various cancers. Using genetic and biochemical approaches, we show that several subunits of the human SWI/SNF complex bind to the tumor suppressor protein p53 in vivo and in vitro. The transactivation f
Histone-modifying enzymes play a pivotal role in gene expression and repression. In human, DOT1L (Dot1-like) is the only known histone H3 lysine 79 methyltransferase. hDOT1L is associated with transcriptional activation, but the general mechanism connecting hDOT1L to active transcription remains largely unknown. Here, we report that hDOT1L interacts with the phosphorylated C-terminal domain of actively transcribing RNA polymerase II (RNAPII) through a region conserved uniquely in multicellular D
Phosphoserine incorporation: A general strategy for producing recombinant histones with site-specific serine phosphorylation is developed by engineering phosphoseryl-tRNA synthetase (SepRS) and elongation factor Tu (EF-Tu; see picture). Serine-phosphorylated nucleosomes provide direct evidence for crosstalk between phosphorylation and acetylation in histones.
cAMP response element-binding protein-binding protein (CBP) is a eucaryotic transcriptional co-activator that contains multiple protein-protein interaction domains for association with various transcription factors, components of the basal transcriptional apparatus, and other co-activator proteins. Here, we report that CBP is also a co-activator of the human papillomavirus (HPV) E2 protein, which is a sequence-specific transcription/replication factor. We provide biochemical, genetic, and functi
Octopus-toolkit is a stand-alone application for retrieving and processing large sets of next-generation sequencing (NGS) data with a single step. Octopus-toolkit is an automated set-up-and-analysis pipeline utilizing the Aspera, SRA Toolkit, FastQC, Trimmomatic, HISAT2, STAR, Samtools, and HOMER applications. All the applications are installed on the user's computer when the program starts. Upon the installation, it can automatically retrieve original files of various epigenomic and transcripto
The transcriptional regulation of the human telomerase reverse transcriptase (hTERT) gene is a critical step in transformation and differentiation. Human papillomavirus E2 protein inhibits cell growth in HPV-infected cells and triggers apoptosis in HeLa cells. Because E2 induces cell growth suppression and senescence, we hypothesize that the protein may modulate cellular gene expression related to these processes. In this report, we demonstrate that E2 inhibits the hTERT promoter. The mapping of
Abstract Previous studies have revealed that nucleosomes impede elongation of RNA polymerase II (RNAPII). Recent observations suggest a role for ATP-dependent chromatin remodellers in modulating this process, but direct in vivo evidence for this is unknown. Here using fission yeast, we identify Fun30 Fft3 as a chromatin remodeller, which localizes at transcribing regions to promote RNAPII transcription. Fun30 Fft3 associates with RNAPII and collaborates with the histone chaperone, FACT, which fa
Triple-negative breast cancer (TNBC) is a malignant cancer subtype with a high risk of recurrence and an aggressive phenotype compared to other breast cancer subtypes. Although many breast cancer studies conducted to date have investigated genetic variations and differential target gene expression, how 3D chromatin architectures are reorganized in TNBC has been poorly elucidated. Here, using in situ Hi-C technology, we characterized the 3D chromatin organization in cells representing five distin
Dot1 (disruptor of telomeric silencing-1, DOT1L in humans) is the only known enzyme responsible for histone H3 lysine 79 methylation (H3K79me) and is evolutionarily conserved in most eukaryotes. Yeast Dot1p lacks a SET domain and does not methylate free histones and thus may have different actions with respect to other histone methyltransferases. Here we show that Dot1p displays histone chaperone activity and regulates nucleosome dynamics via histone exchange in yeast. We show that a methylation
p300/CREB-binding protein-associated factor (p/CAF), a transcriptional co-activator, interacts with co-activator p300/CBP and acidic transcription factors. p/CAF mediates transcriptional activation by acetylating nucleosomal histones and cellular factors. Previously we reported that CBP binds to human papillomavirus E2 and activates E2-dependent transcription (Lee, D., Lee, B., Kim, J., Kim, D. W., and Choe, J. (2000)J. Biol. Chem. 275, 7045–7051). Here we show that p/CAF binds to the human papi
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