Repression of ADH1 and ADH3 during zinc deficiency by Zap1-induced intergenic RNA transcripts

Abstract

The transcriptional activator Zap1 induces target gene expression in response to zinc deficiency. We demonstrate that during zinc starvation, Zap1 is required for the repression of ADH1 expression. ADH1 encodes the major zinc-dependent alcohol dehydrogenase that is utilized during fermentation. During zinc starvation, Zap1 binds upstream of the activator Rap1 and induces an intergenic RNA transcript, ZRR1. ZRR1 expression leads to the transient displacement of Rap1 from the ADH1 promoter resulting in ADH1 repression. Using a microarray-based approach, we screened for additional genes repressed by Zap1 intergenic transcripts. We found that ADH3, the major mitochondrial alcohol dehydrogenase, is regulated in a manner similar to ADH1. Thus, during zinc deficiency, Zap1 mediates the repression of two of the most abundant zinc-requiring enzymes.

Physiological and Transcriptional Responses of Saccharomyces cerevisiae to Zinc Limitation in Chemostat Cultures

“…S. cerevisiae contains multiple alcohol dehydrogenases. While the enzymes encoded by ADH1, -2, -3, and -5 all require Zn as a cofactor, Adh4p uses Mg. ADH4 has been shown to be regulated by Zap1p, while expression of the Znrequiring isoenzymes has been reported to be decreased upon Zn depletion (presumably via Rap1p) (8). In agreement with earlier findings, ADH4 was strongly up-regulated in response to Zn limitation irrespective of the aeration conditions.…”

Regulation of Internal Promoters in a Zinc-Responsive Operon Is Influenced by Transcription from Upstream Promoters

“…In other cases, transcriptional interference of tandem promoters may occur through transcription factor dislodgement by advancing RNAP (32)(33)(34). This may also be the case for P2 and P1.…”

Intragenic transcription of a noncoding RNA modulates expression of ASP3 in budding yeast

“…Several recent studies revealed that transcription of ncRNAs plays certain functional roles. The effects of these transcripts could be repressive (Martens et al 2004;Bird et al 2006;Hongay et al 2006;Camblong et al 2007;Houseley et al 2008) or stimulatory (Uhler et al 2007) for transcription. The gene PHO5 represents the first example of transcriptional activation by a ncRNA: In this case, the transcription of an noncoding antisense RNA initiated at the 39 end of the gene activates full-length PHO5 expression (Uhler et al 2007).…”

“…Recent findings in human, mouse, and Saccharomyces cerevisiae demonstrate that these ncRNAs play roles in the regulation of gene expression (Azzalin et al 2007;Houseley et al 2007;Rinn et al 2007;Luke et al 2008;Nagano et al 2008;Pandey et al 2008;Schoeftner and Blasco 2008). ncRNAs exhibit their functions through either the transcribed RNAs (Camblong et al 2007;Martianov et al 2007;Berretta et al 2008;Nishizawa et al 2008;Wang et al 2008) or the action of transcription (Martens et al 2004;Bird et al 2006;Hongay et al 2006;Uhler et al 2007;Houseley et al 2008;Hartzog and Martens 2009). Although ncRNAs are predominantly transcribed in the antisense orientation to repress sense transcripts through RNA-mediated transcriptional gene silencing (Hongay et al 2006;Camblong et al 2007Camblong et al , 2009Berretta et al 2008;Houseley et al 2008), other types of ncRNA-mediated gene regulation have been identified.…”

“…Although ncRNAs are predominantly transcribed in the antisense orientation to repress sense transcripts through RNA-mediated transcriptional gene silencing (Hongay et al 2006;Camblong et al 2007Camblong et al , 2009Berretta et al 2008;Houseley et al 2008), other types of ncRNA-mediated gene regulation have been identified. ncRNAs can be transcribed upstream of a promoter in the sense orientation to repress the downstream gene expression by a transcriptional interference mechanism (Martens et al 2004;Bird et al 2006). Additionally, antisense ncRNAs can promote gene expression through a chromatin-remodeling mechanism (Uhler et al 2007).…”