Archaea possess a eukaryotic-type basal transcription apparatus that is regulated by bacteria-like transcription regulators. A universal and abundant family of transcription regulators are the bacterial/archaeal Lrp-like regulators. The Lrp family is one of the best studied regulator families in archaea, illustrated by investigations of proteins from the archaeal model organisms: Sulfolobus, Pyrococcus, Methanocaldococcus, and Halobacterium. These regulators are extremely versatile in their DNA-binding properties, response to effector molecules, and molecular regulatory mechanisms. Besides being involved in the regulation of the amino acid metabolism, they also regulate central metabolic processes. It appears that these regulatory proteins are also involved in large regulatory networks, because of hierarchical regulations and the possible combinatorial use of different Lrp-like proteins. Here, we discuss the recent developments in our understanding of this important class of regulators. 1. Introduction The response and adaptation to environmental and nutritional changes, which is essential for the fitness and survival of microorganisms, is driven largely by regulation at the transcriptional level. In archaea, the vast majority of proteins that exert transcription regulation by binding the DNA and affecting gene expression are predicted to resemble bacterial classes of transcription regulators [1]. Almost 50% of all thus far identified regulators can be found in archaea and bacteria, while only 1.7% is common between archaea and eukaryotes [2]. Most of these predicted archaeal regulatory proteins possess a helix-turn-helix (HTH) DNA-binding motif, a typical bacterial motif. Intriguingly, archaea have a basal transcription machinery that is homologous to that of eukaryotes, albeit it being a simplified version, as is also the case for other information processes such as replication and translation [3–7]. Both cis and trans elements share homology with their eukaryotic counterparts. Cases in point are the main promoter elements TATA box and factor B recognition element (BRE) on the one hand, and the general transcription factors TATA-binding protein (TBP), transcription factor B (TFB), and the RNA polymerase (RNAP) on the other hand [3, 8]. The unique archaeal RNAP is most reminiscent of the eukaryotic RNAPII, having up to 13 subunits [9–11]. This peculiar hybrid situation raises the question as to how these bacterial-type regulators in archaeal organisms interact with the eukaryotic-like basal transcription machinery. This is especially true for
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