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Agarwal, Suneet

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Agarwal

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Suneet

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Agarwal, Suneet

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2009 - 200912010 - 20112

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Author's Publications: search.filters.isAuthorOfPublication.d49acf3f-9d44-4828-9595-8788f8a68039

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    Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by the MLL Partner TET1
    (American Association for the Advancement of Science, 2009) Tahiliani, Mamta V.; Koh, Kian Peng; Shen, Yinghua; Pastor, William Abraham; Bandukwala, Hozefa S; Brudno, Yevgeny; Agarwal, Suneet; Iyer, Lakshminarayan M.; Liu, David; Aravind, L; Rao, Anjana
    DNA cytosine methylation is crucial for retrotransposon silencing and mammalian development. In a computational search for enzymes that could modify 5-methylcytosine (5mC), we identified TET proteins as mammalian homologs of the trypanosome proteins JBP1 and JBP2, which have been proposed to oxidize the 5-methyl group of thymine. We show here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro. hmC is present in the genome of mouse embryonic stem cells, and hmC levels decrease upon RNA interference–mediated depletion of TET1. Thus, TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC.
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    Reprogramming of T Cells From Human Peripheral Blood
    (Elsevier BV, 2010-07-02) Loh, Yuin-Han; Hartung, Odelya; Li, Hu; Guo, Chunguang; Sahalie, Julie M.; Manos, Philip D.; Urbach, Achia; Heffner, Garrett C.; Grskovic, Marica; Vigneault, Francois; Lensch, Willy; Park, In-Hyun; Agarwal, Suneet; Church, George; Collins, James; Irion, Stefan; Daley, George
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    Somatic coding mutations in human induced pluripotent stem cells
    (Springer Nature, 2011) Gore, A; Li, Z; Fung, HL; Young, J; Agarwal, Suneet; Antosiewicz-Bourget, J; Canto, I; Israel, M; Kiskinis, E; Lee, JH; Loh, YH; Manos, P; Montserrat, N; Wilbert, M; Yu, J; Kirkness, E; Belmonte, JCI; Daley, GQ; Eggan, Kevin; Rossi, DJ; Thomson, J; Goldstein, LSB; Zhang, K
    Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells. Although DNA factors are integrated during some reprogramming methods, it is unknown whether the genome remains unchanged at the single nucleotide level. Here we show that 22 human induced pluripotent stem (hiPS) cell lines reprogrammed using five different methods each contained an average of five protein-coding point mutations in the regions sampled (an estimated six protein coding point mutations per exome). The majority of these mutations were non-synonymous, nonsense, or splice variants, and were enriched in genes mutated or having causative effects in cancers. At least half of these reprogramming-associated mutations pre-existed in fibroblast progenitors at low frequencies, while the rest were newly occurring during or after reprogramming. Thus, hiPS cells acquire genetic modifications in addition to epigenetic modifications. Extensive genetic screening should become a standard procedure to ensure hiPS safety before clinical use.