Mamta Tahiliani, PhD

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Assistant Professor of Biochemistry
2009, PhD Harvard Medical School

LAB WEBSITE:
Tahiliani Lab
KEYWORDS:
Stem cells, cancer, Chromatin, DNA Methylation and Hydroxymethylation, Genomic Stability

Contact Information

Skirball Institute of Biomolecular Medicine
540 First Ave
2nd Floor, Lab 7
New York, NY 10016
Tel: (212) 263-2854
E-mail: Mamta.Tahiliani@med.nyu.edu
Website: http://www.med.nyu.edu/biosketch/tahilm01#


Interconnection between DNA modifications and genomic regulation.

 

5-methylcytosine is a minor base in mammalian DNA, which plays a disproportionately critical role in development. DNA methylation is very dynamic during embryogenesis and is vital for parental imprinting, X inactivation, silencing of endogenous retroviruses as well as the regulation of genomic stability. De novo methylation and demethylation also occur in somatic cells during differentiation, tumorigenesis and aging. In contrast to the established relation between DNA methylation, DNA methyltransferases and gene silencing, the enzymes and processes regulating DNA demethylation are not well understood. We have recently discovered that TET1 catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (hmC). We also found that hmC can be detected in the genome of mouse ES cells, and that both TET1 levels and hmC levels decline when ES cells are differentiated. These results suggest that hmC is a normal constituent of mammalian DNA, and identify TET1 as an enzyme with a potential role in epigenetic regulation through modification of 5mC. This study described a new class of enzymes that catalyze a new modification of DNA and alters our perception of how DNA methylation status may be regulated in cells. The description of the regulated conversion of 5mC to hmC raises an enormous number of new questions that are of pressing importance. The goal of my laboratory is to integrate hmC into known pathways of 5mC metabolism and to determine how hmC exerts its influence on the genome with the ultimate goal of understanding the role that 5mC and hmC plays in pluripotency and genomic stability.

Selected Publications: 

Koh, KP; Yabuuchi, A; Rao, S; Huang, Y; Cunniff, K; Nardone, J; Laiho, A; Tahiliani, M; Sommer, CA; Mostoslavsky, G; Lahesmaa, R; Orkin, SH; Rodig, SJ; Daley, GQ; Rao, A. Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells.  Cell Stem Cell 2011 Feb;8(2):200-213. PMID: 21295276

Pastor WA, Pape UJ, Huang Y, Henderson HR, Lister R, Ko M, McLoughlin EM, Brudno Y, Mahapatra S, Kapranov P, Tahiliani M, Daley GQ, Liu XS, Ecker JR, Milos PM, Agarwal S, Rao A. (2011) “Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells.” Nature. May 19;473(7347):394-7. Epub 2011 May 8. PMID: 21552279

Koh KP, Yabuuchi A, Rao S, Huang Y, Cunniff K, Nardone J, Laiho A, Tahiliani M, Sommer CA, Mostoslavsky G, Lahesmaa R, Orkin SH, Rodig SJ, Daley GQ, Rao A. (2011) “Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells.” Cell Stem Cell. Feb 4;8(2):200-13. PMID: 21295276

Ko M, Huang Y, Jankowska AM, Pape UJ, Tahiliani M, Bandukwala HS, An J, Lamperti ED, Koh KP, Ganetzky R, Liu XS, Aravind L, Agarwal S, Maciejewski JP, Rao A. (2010) “Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2.” Nature. Dec 9;468(7325):839-43. PMID: 21057493

Huang Y, Pastor WA, Shen Y, Tahiliani M, Liu DR, Rao A. (2010) “The behaviour of 5-hydroxymethylcytosine in bisulfite sequencing.” PLoS One  5: 8888. PMID: 20126651

Mamta Tahiliani, Kian Peng Koh, Yinghua Shen, William A. Pastor, Hozefa Bandukwala, Yevgeny Brudno, Suneet Agarwal, Lakshminarayan M. Iyer, David R. Liu, L. Aravind, Anjana Rao. (2009) “Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by the MLL fusion partner, TET1.” Science 324 (5929): 930-5. PMID: 19372391

Lakshminarayan M. Iyer, Mamta Tahiliani, Anjana Rao, L. Aravind. (2009) “Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids.” Cell Cycle  8(11): 1698-1710. PMID: 19411852

Ansel KM, Pastor WA, Rath N, Lapan AD, Glasmacher E, Wolf C, Smith LC, Papadopoulou N, Lamperti ED, Tahiliani M, Ellwart J, Shi YJ, Kremmer E, Rao A, Heissmeyer V. (2008)  “Mouse ERI-1 interacts with the ribosome and catalyzes 5.8S rRNA processing.” Nature Structural Biology 15(5): 523-30. PMID: 18438418

Tahiliani M, Mei P, Fang R, Leonor T, Rutenberg M, Shimizu F, Li J, Rao A, Shi Y. (2007) “The Histone H3K4 Demethylase SMCX Links REST Target Genes to X-Linked Mental Retardation.” Nature  447: 601-5. PMID: 17468742