title: Functional specialization of two paralogous TAF12 variants by their selective association with SAGA and TFIID transcriptional regulatory complexes.
abstract: TATA box-binding protein (TBP)-associated factors (TAFs), evolutionarily conserved from yeast to humans, play a central role during transcription initiation. A subset of TAF proteins is shared in transcription factor II D (TFIID) and SAGA transcription regulatory complexes. Although higher eukaryotes contain multiple TAF variants that specify tissue- and developmental stage-specific organization of TFIID or SAGA complexes, in unicellular genomes, however, each TAF is encoded by a single gene. Surprisingly, we found that the genome ofCandida albicans, the predominant human fungal pathogen, contains two paralogousTAF12genes,CaTAF12LandCaTAF12, encoding H2B-like histone-fold domain-containing variants. Of the available fungal genome sequences, only seven other closely related diploid pathogenicCandidagenomes encode the twoTAF12paralogs. Using affinity purifications fromC. albicanscell extracts, we demonstrate that CaTAF12L uniquely associates with the SAGA complex and CaTAF12 associates with the TFIID complex. We further show thatCaTAF12, but notCaTAF12L, is essential forC. albicansgrowth. Conditional depletion of the two TAF12 variant proteins caused distinct cellular and colony phenotypes. Together our results define a specialized organization of the TAF12 variants and non-redundant roles for the twoTAF12variants in the unicellularC. albicansgenome.
authors.affiliation: From the Laboratory of Eukaryotic Gene Regulation, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Ishani
authors.initials: I
authors.lastname: Sinha
authors.affiliation: From the Laboratory of Eukaryotic Gene Regulation, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Shambhu
authors.initials: S
authors.lastname: Kumar
authors.affiliation: From the Laboratory of Eukaryotic Gene Regulation, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Poonia
authors.affiliation: From the Laboratory of Eukaryotic Gene Regulation, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Sonal
authors.initials: S
authors.lastname: Sawhney
authors.affiliation: From the Laboratory of Eukaryotic Gene Regulation, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India nat0200@mail.jnu.ac.in.
authors.forename: Krishnamurthy
authors.initials: K
authors.lastname: Natarajan
mesh_terms: D002176:Candida albicans / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005816:Genetic Complementation Test; D016681:Genome, Fungal; D006801:Humans; D035362:Transcription Factor TFIID / Q000235:genetics / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D035362:Transcription Factor TFIID
keywords: Candida albicans; SAGA; TAF12; TFIID; fungi; gene regulation; transcription regulation; transcriptional coactivator