Hypothetical protein Rv3423.1 of Mycobacterium tuberculosis is a histone acetyltransferase

Jose, Leny and Ramachandran, Ranjit and Bhagavat, Raghu and Gomez, Roshna Lawrence and Chandran, Aneesh and Raghunandanan, Sajith and Omkumar, Ramakrishnapillai Vyomakesannair and Chandra, Nagasuma and Mundayoor, Sathish and Kumar, Ramakrishnan Ajay (2016) Hypothetical protein Rv3423.1 of Mycobacterium tuberculosis is a histone acetyltransferase. In: FEBS JOURNAL, 283 (2). pp. 265-281.

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Abstract

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:	Journal Article
Publication:	FEBS JOURNAL
Publisher:	WILEY-BLACKWELL
Additional Information:	Copy right for this article belongs to the WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Keywords:	chromatin; histone acetyltransferase; macrophage; Mycobacterium tuberculosis; nucleomodulin
Department/Centre:	Division of Information Sciences (Doesn't exist now) > BioInformatics Centre
Date Deposited:	17 Feb 2016 05:27
Last Modified:	17 Feb 2016 05:27
URI:	http://eprints.iisc.ac.in/id/eprint/53238

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