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Mycobacteria modulate host epigenetic machinery by Rv1988 methylation of a non-tail arginine of histone H3

Author

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  • Imtiyaz Yaseen

    (CDFD, Nampally
    Graduate Studies, Manipal University)

  • Prabhjot Kaur

    (National Institute of Immunology)

  • Vinay Kumar Nandicoori

    (National Institute of Immunology)

  • Sanjeev Khosla

    (CDFD, Nampally)

Abstract

Mycobacteria are successful pathogens that modulate the host immune response through unclear mechanisms. Here we show that Rv1988, a secreted mycobacterial protein, is a functional methyltransferase that localizes to the host nucleus and interacts with chromatin. Rv1988 methylates histone H3 at H3R42 and represses the genes involved in the first line of defence against mycobacteria. H3R42me2, a non-tail histone modification, is present at the entry and exit point of DNA in the nucleosome and not within the regulatory sites in the N-terminal tail. Rv1988 deletion in Mycobacterium tuberculosis reduces bacterial survival in the host, and experimental expression of M. tuberculosis Rv1988 in non-pathogenic Mycobacterium smegmatis negatively affects the health of infected mice. Thus, Rv1988 is an important mycobacterial virulence factor, which uses a non-canonical epigenetic mechanism to control host cell transcription.

Suggested Citation

  • Imtiyaz Yaseen & Prabhjot Kaur & Vinay Kumar Nandicoori & Sanjeev Khosla, 2015. "Mycobacteria modulate host epigenetic machinery by Rv1988 methylation of a non-tail arginine of histone H3," Nature Communications, Nature, vol. 6(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9922
    DOI: 10.1038/ncomms9922
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    Cited by:

    1. Lihua Qiang & Yong Zhang & Zehui Lei & Zhe Lu & Shasha Tan & Pupu Ge & Qiyao Chai & Mengyuan Zhao & Xinwen Zhang & Bingxi Li & Yu Pang & Lingqiang Zhang & Cui Hua Liu & Jing Wang, 2023. "A mycobacterial effector promotes ferroptosis-dependent pathogenicity and dissemination," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Prakruti R. Singh & Venkatareddy Dadireddy & Shubha Udupa & Shashwath Malli Kalladi & Somnath Shee & Sanjeev Khosla & Raju S. Rajmani & Amit Singh & Suryanarayanarao Ramakumar & Valakunja Nagaraja, 2023. "The Mycobacterium tuberculosis methyltransferase Rv2067c manipulates host epigenetic programming to promote its own survival," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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