title: The global regulator Ncb2 escapes from the core promoter and impacts transcription in response to drug stress in Candida albicans.
abstract: Ncb2, the β subunit of NC2 complex, a heterodimeric regulator of transcription was earlier shown to be involved in the activated transcription of CDR1 gene in azole resistant isolate (AR) of Candida albicans. This study examines its genome-wide role by profiling Ncb2 occupancy between genetically matched pair of azole sensitive (AS) and AR clinical isolates. A comparison of Ncb2 recruitment between the two isolates displayed that 29 genes had higher promoter occupancy of Ncb2 in the AR isolate. Additionally, a host of genes exhibited exclusive occupancy of Ncb2 at promoters of either AR or AS isolate. The analysis also divulged new actors of multi-drug resistance, whose transcription was activated owing to the differential occupancy of Ncb2. The conditional, sequence-specific positional escape of Ncb2 from the core promoter in AS isolate and its preferential recruitment to the core promoter of certain genes in AR isolates was most noteworthy means of transcription regulation. Together, we show that positional rearrangement of Ncb2 resulting in either activation or repression of gene expression in response to drug-induced stress, represents a novel regulatory mechanism that opens new opportunities for therapeutic intervention to prevent development of drug tolerance in C. albicans cells.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India.|Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi-110067, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Shariq
authors.affiliation: Department of Microbiology, Monash University, VIC, Australia.
authors.forename: Sanjiveeni
authors.initials: S
authors.lastname: Dhamgaye
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India.|Rajiv Gandhi Institute of I.T and Biotechnology, Bharati Vidyapeeth University, Pune-411045, India.
authors.forename: Remya
authors.initials: R
authors.lastname: Nair
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Goyal
authors.affiliation: Molecular Aging Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi-110067, India.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Jain
authors.affiliation: Molecular Aging Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi-110067, India.
authors.forename: Arnab
authors.initials: A
authors.lastname: Mukhopadhyay
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India.
authors.forename: Alok K
authors.initials: AK
authors.lastname: Mondal
authors.affiliation: Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi-110067, India.
authors.forename: Gauranga
authors.initials: G
authors.lastname: Mukhopadhyay
authors.affiliation: Amity Institute of Integrative Sciences and Health and Amity Institute of Biotechnology, Amity University, Haryana-122413, India.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Prasad
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D001483:Base Sequence; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D005656:Fungal Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D016681:Genome, Fungal; D011401:Promoter Regions, Genetic; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D016385:TATA Box / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins