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譚賢明(Bertrand Tan)

譚賢明 (Bertrand Tan)

職稱

教授

最高學歷

國立台灣大學分子醫學研究所 (Ph.D. National Taiwan University, Taiwan)

E-mail

btan@mail.cgu.edu.tw

電話:

+886-3-211-8800 ext.5067

傳真

+886-3-211-8700

實驗室

染色質與表觀基因實驗室

專長

生物化學、蛋白質體學、分子細胞學

研究方向及研究室特色

真核細胞的DNA與其纏繞的組蛋白形成一特殊結構稱為染色質。染色質結構上的鬆緊程度,以及位於染色質上的非組蛋白因子(non-histone proteins),緊密的調控著與DNA相關之生物過程(DNA複製、轉錄、修復等)。細胞具有多種染色質調控蛋白及相關分子機制,透過修飾組蛋白或DNA、重整染色質、或透過特定組蛋白密碼(histone code)來調控染色質結構,進而影響之後的生理步驟。由於這一類型調控染色質的機制不是由基因體序列中的資訊來主導,因此被統稱為表觀遺傳調控(epigenetic regulation)。此類調控因子的功能及活性機轉方面的研究,為「染色質/表觀基因體學」學門之重要主題,我們希望利用整合性的研究系統,更進一步的將染色質結構調控及其相關蛋白,與細胞生長、細胞致癌、以及個體發育作一個連結。

The field of chromatin biology/epigenomics has been a fascinating area of research inquiry in the last decade or so mainly due to the isolation and identification of a myriad of chromatin structure modulators. Through remodeling (or further packaging) or modification of the nucleosomal assembly, or establishing particular histone code or DNA methylation pattern, these types of “epigenetic regulator” activities have proven intrinsically vital to the control of gene expression and DNA structure maintenance, and ultimately, cell physiology. My research is focused mainly on several novel chromatin-associated factors, all of which have distinct yet largely uncharacterized epigenetic roles during different chromatin-based processes:

EDD (E3 isolated by differential display), the mammalian ortholog of the Drosophila melanogaster hyperplastic disc gene (hyd). As a HECT domain-containing protein, EDD may be involved in the ubiquitination cascade that catalyzes the covalent attachment of ubiquitin to specific substrate.
AND-1 (acidic nucleoplasmic DNA-binding protein) is an acidic, nucleoplasmic protein that contains a WD40 domain at amino-terminus and a DNA-binding HMG-box at carboxy-terminus. The cellular role of AND-1 is still largely unknown.
Elongator is a highly conserved transcription elongation factor complex composed of six subunits, Elp1-6. It has been suggested that the histone acetyltransferase (HAT) activity of one of the subunits (Elp3) may assist RNAPII during the elongation phase of chromatin transcription.
FACT (facilitates chromatin transcription). It has been postulated that the heterodimeric FACT complex acts as a core activity that, when in conjunction with pathway-specific cofactors, mediates chromatin loosening during the progression of different DNA-metabolizing events.

The field of chromatin biology/functional epigenomics focuses on the functional integration of many signaling pathways and different chromatin-associated enzymatic or structural factors. Therefore, to thoroughly characterize the functions of our target chromatin modifiers, we are undertaking a multi-disciplinary scheme entailing various tools and methods:

  1. An integrated, functional genomic-based approach based on powerful methods such as ChIP-on-chip, microarray, TF-TF array, and interactomic/proteomic analyses. 
  2. A cell biology/developmental biology approach, including techniques such as immunocytochemistry, siRNA-mediated gene knock down, cell cycle profiling, and fly genetic. 

Through such combinatorial experimental design, we are hoping to systematically explore and answer some of the key questions revolving these target proteins as well as other epigenetic regulators in general:

  1. Global identification of transcriptional targets and chromatin binding sites
  2. “Histone code” alteration/epigenetic regulation at targeted loci
  3. Functional interaction and cooperation among different regulators and co-regulators during chromatin remodeling and gene expression
  4. Understanding the physiological (or patho-physiological) significance of these proteins in the contexts of cell cycle progression, tumorigenesis and Drosophila development

論文與著作

Publications:

  1. Wang YH, Tsay YG, Tan BC, Lo WY, Lee SC. Identification and characterization of a novel p300-mediated p53 acetylation site, lysine 305. J Biol Chem. 2003 Jul 11;278(28):25568-76. (SCI)
  2. Tan BC, Lee SC. Nek9, a novel FACT-associated protein, modulates interphase progression. J Biol Chem. 2004 Mar 5;279(10):9321-30. (SCI)
  3. Tan BC, Chien CT, Hirose S, Lee SC. Functional cooperation between FACT and MCM helicase facilitates initiation of chromatin DNA replication. EMBO J. 2006 Sep 6;25(17):3975-85. (SCI)
  4. Liu H*, Tan BC*, Tseng KH, Chuang CP, Yeh CW, Chen KD, Lee SC, and Yung BYM. NPM acts as a novel AP-2α-binding transcriptional corepressor during cell differentiation. EMBO Rep. 2007 April 1; 8 (4): 394-400. (*equal contribution) (SCI)

生醫新知

當基因不再是命運的主導者–淺談表觀遺傳學研究