Molecular mechanism of heme signaling in yeast: the transcriptional activator Hap1 serves as the key mediator

Abstract

Heme is a key molecule in mediating the effects of oxygen on various molecular and cellular processes in many living organisms. In the yeast Saccharomyces cerevisiae, heme serves as a secondary signal for oxygen; intracellular heme synthesis directly correlates with oxygen tension in the environment. In yeast, oxygen sensing and heme signaling are primarily mediated by the heme activator protein Hap1, which, in response to heme, activates the transcription of genes required for respiration and for controlling oxidative damage. Heme regulation of many genes required for anaerobic growth is mediated by the aerobic repressor Rox1, whose expression is controlled by heme. In this review, we summarize recent knowledge about (i) how heme synthesis may be controlled by oxygen tension, (ii) how heme precisely and stringently controls Hap1 activity and (iii) whether other transcriptional activators can also mediate heme action.

Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases

“…The diverse regulatory roles of heme in living organisms 682 npg many fundamental biological processes [11][12][13][14]. Heme is essential for the transport and storage of oxygen, the generation of cellular energy by respiration, the synthesis and degradation of sterols, lipids and neurotransmitters and for controlling oxidative damage.…”

Regulation of the HAP1 gene involves positive actions of histone deacetylases

“…The yeast heme activator protein Hap1 is an important regulator mediating oxygen and heme regulation [1][2][3][4]. Previous ChIP-chip studies have identified >200 genes, to which Hap1 can bind and regulate [5,6].…”

“…This points to the potential of the Hap1 protein in controlling transcription of diverse genes. Hap1 not only activates transcription of many genes involved in respiration and in controlling oxidative damage, in response to heme or oxygen, but it also represses certain genes, such as its own gene [4,7]. Interestingly, Hap1 activates transcription in a heme-dependent manner, whereas it represses the HAP1 gene in a heme-independent manner [4,7,8].…”

“…Hap1 not only activates transcription of many genes involved in respiration and in controlling oxidative damage, in response to heme or oxygen, but it also represses certain genes, such as its own gene [4,7]. Interestingly, Hap1 activates transcription in a heme-dependent manner, whereas it represses the HAP1 gene in a heme-independent manner [4,7,8]. The mechanism of heme-dependent transcriptional activation by Hap1 has been well studied [4,[9][10][11].…”

“…Interestingly, Hap1 activates transcription in a heme-dependent manner, whereas it represses the HAP1 gene in a heme-independent manner [4,7,8]. The mechanism of heme-dependent transcriptional activation by Hap1 has been well studied [4,[9][10][11]. Previous studies have shown that heme regulation of Hap1 activity requires molecular chaperones Hsp90, Hsp70 and its cochaperones Ydj1 and Sro9 [12][13][14][15][16].…”