Epigenetic regulation of transcription and virulence in Trypanosoma cruzi by O-linked thymine glucosylation of DNA.


:Unlike other eukaryotes, the protein-coding genes of Trypanosoma cruzi are arranged in large polycistronic gene clusters transcribed by polymerase II (Pol II). Thus, it is thought that trypanosomes rely solely on posttranscriptional processes to regulate gene expression. Here, we show that the glucosylated thymine DNA base (β-d-glucosyl-hydroxymethyluracil or base J) is present within sequences flanking the polycistronic units (PTUs) in T. cruzi. The loss of base J at sites of transcription initiation, via deletion of the two enzymes that regulate base J synthesis (JBP1 and JBP2), correlates with an increased rate of Pol II transcription and subsequent genome-wide increase in gene expression. The affected genes include virulence genes, and the resulting parasites are defective in host cell invasion and egress. These studies indicate that base J is an epigenetic factor regulating Pol II transcription initiation in kinetoplastids and provides the first biological role of the only hypermodified DNA base in eukaryotes.


Mol Cell Biol


Ekanayake DK,Minning T,Weatherly B,Gunasekera K,Nilsson D,Tarleton R,Ochsenreiter T,Sabatini R




Has Abstract


2011-04-01 00:00:00














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    abstract::We investigated the role of RNA polymerase II (pol II) carboxy-terminal domain (CTD) phosphorylation in pre-mRNA processing coupled and uncoupled from transcription in Xenopus oocytes. Inhibition of CTD phosphorylation by the kinase inhibitors 5,6-dichloro-1beta-D-ribofuranosyl-benzimidazole and H8 blocked transcripti...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Bird G,Zorio DA,Bentley DL

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    abstract::Fusions between the TRM1 gene of Saccharomyces cerevisiae and COXIV or DHFR were made to examine the mitochondrial targeting signals of N2,N2-dimethylguanosine-specific tRNA methyltransferase [tRNA (m2(2)G)dimethyltransferase]. This enzyme is responsible for the modification of both mitochondrial and cytoplasmic tRNAs...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Ellis SR,Hopper AK,Martin NC

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    abstract::Independent of its antiapoptotic function, Bcl-2 can, through an undetermined mechanism, retard entry into the cell cycle. Cell cycle progression requires the phosphorylation by cyclin-dependent kinases (Cdks) of retinoblastoma protein (pRB) family members to free E2F transcription factors. We have explored whether re...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Vairo G,Soos TJ,Upton TM,Zalvide J,DeCaprio JA,Ewen ME,Koff A,Adams JM

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    abstract::The death-associated protein (DAP) kinase family includes three protein kinases, DAP kinase, DAP kinase-related protein 1, and ZIP kinase, which display 80% amino acid identity within their catalytic domains and are functionally linked to common subcellular changes occurring during cell death, such as the process of m...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Shani G,Marash L,Gozuacik D,Bialik S,Teitelbaum L,Shohat G,Kimchi A

    更新日期:2004-10-01 00:00:00

  • The 5' untranslated sequence of the c-sis/platelet-derived growth factor 2 transcript is a potent translational inhibitor.

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Rao CD,Pech M,Robbins KC,Aaronson SA

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    abstract::Woodchucks infected with woodchuck hepatitis virus (WHV) and ground squirrels infected with ground squirrel hepatitis virus (GSHV) both develop hepatocellular carcinoma (HCC), but WHV-associated tumors arise more frequently and much earlier in life. These differences are preserved when the oncogenic potentials of the ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Hansen LJ,Tennant BC,Seeger C,Ganem D

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Rozen F,Pelletier J,Trachsel H,Sonenberg N

    更新日期:1989-09-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Langer SJ,Bortner DM,Roussel MF,Sherr CJ,Ostrowski MC

    更新日期:1992-12-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Kerbel RS,Lagarde AE,Dennis JW,Donaghue TP

    更新日期:1983-04-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Branciforte D,Martin SL

    更新日期:1994-04-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Gwynn B,Lyford KA,Birkenmeier EH

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Morgan MA,Mould AW,Li L,Robertson EJ,Bikoff EK

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Brissette JL,Kumar NM,Gilula NB,Dotto GP

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    authors: Escher D,Bodmer-Glavas M,Barberis A,Schaffner W

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    authors: Catala F,Wanner R,Barton P,Cohen A,Wright W,Buckingham M

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Smith HE,Mitchell AP

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    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Hsieh CL

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    abstract::The androgen receptor (AR) is a ligand-activated transcription factor that interacts with coregulatory proteins during androgen-dependent gene regulation. Melanoma antigen gene protein 11 (MAGE-11) is an AR coregulator that specifically binds the AR NH(2)-terminal FXXLF motif and modulates the AR NH(2)- and carboxyl-t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Bai S,Wilson EM

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Zhang W,Kadam S,Emerson BM,Bieker JJ

    更新日期:2001-04-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Brown PC,Tlsty TD,Schimke RT

    更新日期:1983-06-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Atkin AL,Roy KL,Bell JB

    更新日期:1990-08-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Zheng S,Wyrick JJ,Reese JC

    更新日期:2010-07-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Grayson J,Williams RS,Yu YT,Bassel-Duby R

    更新日期:1995-04-01 00:00:00