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Hypothetical protein Rv3423.1 of Mycobacterium tuberculosis is a histone acetyltransferase
Author(s) -
Jose Leny,
Ramachandran Ranjit,
Bhagavat Raghu,
Gomez Roshna Lawrence,
Chandran Aneesh,
Raghunandanan Sajith,
Omkumar Ramakrishnapillai Vyomakesannair,
Chandra Nagasuma,
Mundayoor Sathish,
Kumar Ramakrishnan Ajay
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13566
Subject(s) - histone acetyltransferase , mycobacterium smegmatis , biology , acetyltransferase , chromatin immunoprecipitation , histone , chromatin , recombinant dna , acetylation , mycobacterium tuberculosis , histone h1 , microbiology and biotechnology , sap30 , gene expression , gene , biochemistry , promoter , tuberculosis , medicine , pathology
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.