Abstract
The CCAAT-binding complex (CBC) is a heterotrimeric transcription factor which is widely conserved in eukaryotes. In the model yeast S. cerevisiae, CBC positively controls the expression of respiratory pathway genes. This role involves interactions with the regulatory subunit Hap4. In many pathogenic fungi, CBC interacts with the HapX regulatory subunit to control iron homeostasis. HapX is a bZIP protein which only shares with Hap4 the Hap4Like domain (Hap4L) required for its interaction with CBC. Here, we show that CBC has a dual role in the pathogenic yeast C. glabrata. It is required, along with Hap4, for the constitutive expression of respiratory genes and it is also essential for the iron stress response, which is mediated by the Yap5 bZIP transcription factor. Interestingly, Yap5 contains a vestigial Hap4L domain. The mutagenesis of this domain severely reduced Yap5 binding to its targets and compromised its interaction with Hap5. Hence, Yap5, like HapX in other species, acts as a CBC regulatory subunit in the regulation of iron stress response. This work reveals new aspects of iron homeostasis in C. glabrata and of the evolution of the role of CBC and Hap4L-bZIP proteins in this process.
Highlights
This domain in HapX proteins remains to be elucidated since HapX and Hap[43] clearly bind CCAAT motifs indirectly through their interaction with CCAAT-binding complex (CBC), rather than YREs11, 20, 24
In S. cerevisiae, in contrast to C. albicans and Aspergillus sp., CBC does not seem to contribute to the global iron starvation response[26], but its role in iron homeostasis has been poorly investigated in this species[27]
We identified a part of the transcriptional network associated with CBC, more the Hap[5] subunit, in the pathogenic yeast C. glabrata
Summary
This domain in HapX proteins remains to be elucidated since HapX and Hap[43] clearly bind CCAAT motifs indirectly through their interaction with CBC, rather than YREs11, 20, 24. HapX contributes to the DNA binding specificity of the CBC-HapX complex in A. nidulans and the bZIP domain is absolutely required for the regulation of transcription by Hap[43] in C. albicans[18, 25]. A potential ortholog of Hap43/HapX, named Yap[7], has been identified in S. cerevisiae[18, 23], but it is not directly involved in iron starvation or iron excess responses[21]. We observed that Hap[5] directly controls the iron stress response mediated by the Yap[5] bZip transcription factor. Our results revealed a key role of CBC in the iron stress response of C. glabrata and identified Yap[5] as a new CBC regulatory subunit
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
