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Leny, Jose and Ranjith, Ramachandran and Raghu, Bhagavat and Roshna Lawrence, Gomez and Aneesh, Chandran and Sajith, Raghunandanan and RV, Omkumar and Nagasuma, Chandra and Sathish, Mundayoor and R, AjayKumar (2016) Hypothetical protein Rv3423.1 of Mycobacterium tuberculosis is a histone acetyltransferase. The FEBS journal, 283(2). pp. 265-81. ISSN 1742-4658

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We isolated an 8 kDa mycobacterial hypothetical protein, Rv3423.1, from the chromatin of human macrophages infected with Mycobacterium tuberculosis H37Rv. Bioinformatics predictions followed by in vitro biochemical assays with purified recombinant protein showed that Rv3423.1 is a novel histone acetyltransferase that acetylates histone H3 at the K9/K14 positions. Transient transfection of macrophages containing GFP-tagged histone H1 with RFP-tagged Rv3423.1 revealed that the protein co-localizes with the chromatin in the nucleus. Co-immunoprecipitation assays confirmed that the Rv3423.1-histone interaction is specific. Rv3423.1 protein was detected in the culture filtrate of virulent but not avirulent M. tuberculosis. Infection of macrophages with recombinant Mycobacterium smegmatis constitutively expressing Rv3423.1 resulted in a significant increase in the number of intracellular bacteria. However, the protein did not seem to offer any growth advantage to free-living recombinant M. smegmatis. It is highly likely that, by binding to the host chromatin, this histone acetyltransferase from M. tuberculosis may manipulate the expression of host genes involved in anti-inflammatory responses to evade clearance and to survive in the intracellular environment.

Item Type: Article
Uncontrolled Keywords: Mycobacterium tuberculosis; chromatin; histone acetyltransferase; macrophage; nucleomodulin
Subjects: Tropical Disease Biology
Depositing User: Rgcb Library
Date Deposited: 26 Dec 2016 06:05
Last Modified: 27 Dec 2016 07:13
URI: http://rgcb.sciencecentral.in/id/eprint/61

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