title: Hypothetical protein Rv3423.1 of Mycobacterium tuberculosis is a histone acetyltransferase.
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.
authors.affiliation: Mycobacterium Research Group, Tropical Disease Biology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Leny
authors.initials: L
authors.lastname: Jose
authors.affiliation: Mycobacterium Research Group, Tropical Disease Biology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Ramachandran
authors.affiliation: Bioinformatics Centre, Indian Institute of Science, Bangalore, India.
authors.forename: Raghu
authors.initials: R
authors.lastname: Bhagavat
authors.affiliation: Mycobacterium Research Group, Tropical Disease Biology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Roshna Lawrence
authors.initials: RL
authors.lastname: Gomez
authors.affiliation: Mycobacterium Research Group, Tropical Disease Biology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Aneesh
authors.initials: A
authors.lastname: Chandran
authors.affiliation: Mycobacterium Research Group, Tropical Disease Biology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Sajith
authors.initials: S
authors.lastname: Raghunandanan
authors.affiliation: Neurobiology Group, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Ramakrishnapillai Vyomakesannair
authors.initials: RV
authors.lastname: Omkumar
authors.affiliation: Bioinformatics Centre, Indian Institute of Science, Bangalore, India.
authors.forename: Nagasuma
authors.initials: N
authors.lastname: Chandra
authors.affiliation: Mycobacterium Research Group, Tropical Disease Biology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Sathish
authors.initials: S
authors.lastname: Mundayoor
authors.affiliation: Mycobacterium Research Group, Tropical Disease Biology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Ramakrishnan Ajay
authors.initials: RA
authors.lastname: Kumar
mesh_terms: D000105:Acetyl Coenzyme A / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D003198:Computer Simulation; D015964:Gene Expression Regulation, Bacterial; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D020102:Mycobacterium smegmatis / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000472:pathogenicity; D009243:NAD / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D002843:Chromatin; D006657:Histones; D009243:NAD; D000105:Acetyl Coenzyme A; D051548:Histone Acetyltransferases; C000609237:Rv3423.1 protein, Mycobacterium tuberculosis
keywords: Mycobacterium tuberculosis; chromatin; histone acetyltransferase; macrophage; nucleomodulin