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Evolution of the holozoan ribosome biogenesis regulon.

Brown SJ, Cole MD, Erives AJ - BMC Genomics (2008)

Bottom Line: These results show that this mode of regulation, characterized by an E(CG)-bearing core-promoter, is specific to almost all of the known genes involved in ribosome biogenesis in these genomes.Furthermore, a detailed analysis of 10 fungal genomes shows that this holozoan signature in RiBi genes is not found in hemiascomycete fungi, which evolved their own unique regulatory signature for the RiBi regulon.Furthermore, by comparing divergent bHLH repertoires, we conclude that regulation by Myc but not by other bHLH genes is responsible for the evolutionary maintenance of E(CG) sites across the RiBi suite of genes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756, USA. seth.brown@dartmouth.edu

ABSTRACT

Background: The ribosome biogenesis (RiBi) genes encode a highly-conserved eukaryotic set of nucleolar proteins involved in rRNA transcription, assembly, processing, and export from the nucleus. While the mode of regulation of this suite of genes has been studied in the yeast, Saccharomyces cerevisiae, how this gene set is coordinately regulated in the larger and more complex metazoan genomes is not understood.

Results: Here we present genome-wide analyses indicating that a distinct mode of RiBi regulation co-evolved with the E(CG)-binding, Myc:Max bHLH heterodimer complex in a stem-holozoan, the ancestor of both Metazoa and Choanoflagellata, the protozoan group most closely related to animals. These results show that this mode of regulation, characterized by an E(CG)-bearing core-promoter, is specific to almost all of the known genes involved in ribosome biogenesis in these genomes. Interestingly, this holozoan RiBi promoter signature is absent in nematode genomes, which have not only secondarily lost Myc but are marked by invariant cell lineages typically producing small body plans of 1000 somatic cells. Furthermore, a detailed analysis of 10 fungal genomes shows that this holozoan signature in RiBi genes is not found in hemiascomycete fungi, which evolved their own unique regulatory signature for the RiBi regulon.

Conclusion: These results indicate that a Myc regulon, which is activated in proliferating cells during normal development as well as during tumor progression, has primordial roots in the evolution of an inducible growth regime in a protozoan ancestor of animals. Furthermore, by comparing divergent bHLH repertoires, we conclude that regulation by Myc but not by other bHLH genes is responsible for the evolutionary maintenance of E(CG) sites across the RiBi suite of genes.

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Evolution of shared motifs in opisthokont RiBi core promoters. The promoter gene sets for each species depicted in Figure 4 weres analyzed by MEME to identify common cis-regulatory motifs for each lineage [57,58]. Motifs found in greater than two-thirds of RiBi genes are depicted from left to right (highest scoring motifs to left). The frequency of each motif is expressed as a percentage in the upper left corner. The known fungal motifs RRPE [5,6] and PAC [5-7] are shown in shown in black and blue, respectfully. The holozoan E(CG) motif identified in this work is shown in orange.
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Figure 5: Evolution of shared motifs in opisthokont RiBi core promoters. The promoter gene sets for each species depicted in Figure 4 weres analyzed by MEME to identify common cis-regulatory motifs for each lineage [57,58]. Motifs found in greater than two-thirds of RiBi genes are depicted from left to right (highest scoring motifs to left). The frequency of each motif is expressed as a percentage in the upper left corner. The known fungal motifs RRPE [5,6] and PAC [5-7] are shown in shown in black and blue, respectfully. The holozoan E(CG) motif identified in this work is shown in orange.

Mentions: Importantly, we also failed to find elevated levels of E(CG) in yeast RiBi versus control groups (C1 and CM in Fig. 2). Of relevance, the yeast RiBi genes are known to be regulated by motifs that are distinct from E(CG) [29-31]. We were also unable to find the E(CG)-RiBi signature in other fungal and more distantly related eukaryotic genomes (see Figs. 4, 5 and Methods).


Evolution of the holozoan ribosome biogenesis regulon.

Brown SJ, Cole MD, Erives AJ - BMC Genomics (2008)

Evolution of shared motifs in opisthokont RiBi core promoters. The promoter gene sets for each species depicted in Figure 4 weres analyzed by MEME to identify common cis-regulatory motifs for each lineage [57,58]. Motifs found in greater than two-thirds of RiBi genes are depicted from left to right (highest scoring motifs to left). The frequency of each motif is expressed as a percentage in the upper left corner. The known fungal motifs RRPE [5,6] and PAC [5-7] are shown in shown in black and blue, respectfully. The holozoan E(CG) motif identified in this work is shown in orange.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570694&req=5

Figure 5: Evolution of shared motifs in opisthokont RiBi core promoters. The promoter gene sets for each species depicted in Figure 4 weres analyzed by MEME to identify common cis-regulatory motifs for each lineage [57,58]. Motifs found in greater than two-thirds of RiBi genes are depicted from left to right (highest scoring motifs to left). The frequency of each motif is expressed as a percentage in the upper left corner. The known fungal motifs RRPE [5,6] and PAC [5-7] are shown in shown in black and blue, respectfully. The holozoan E(CG) motif identified in this work is shown in orange.
Mentions: Importantly, we also failed to find elevated levels of E(CG) in yeast RiBi versus control groups (C1 and CM in Fig. 2). Of relevance, the yeast RiBi genes are known to be regulated by motifs that are distinct from E(CG) [29-31]. We were also unable to find the E(CG)-RiBi signature in other fungal and more distantly related eukaryotic genomes (see Figs. 4, 5 and Methods).

Bottom Line: These results show that this mode of regulation, characterized by an E(CG)-bearing core-promoter, is specific to almost all of the known genes involved in ribosome biogenesis in these genomes.Furthermore, a detailed analysis of 10 fungal genomes shows that this holozoan signature in RiBi genes is not found in hemiascomycete fungi, which evolved their own unique regulatory signature for the RiBi regulon.Furthermore, by comparing divergent bHLH repertoires, we conclude that regulation by Myc but not by other bHLH genes is responsible for the evolutionary maintenance of E(CG) sites across the RiBi suite of genes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756, USA. seth.brown@dartmouth.edu

ABSTRACT

Background: The ribosome biogenesis (RiBi) genes encode a highly-conserved eukaryotic set of nucleolar proteins involved in rRNA transcription, assembly, processing, and export from the nucleus. While the mode of regulation of this suite of genes has been studied in the yeast, Saccharomyces cerevisiae, how this gene set is coordinately regulated in the larger and more complex metazoan genomes is not understood.

Results: Here we present genome-wide analyses indicating that a distinct mode of RiBi regulation co-evolved with the E(CG)-binding, Myc:Max bHLH heterodimer complex in a stem-holozoan, the ancestor of both Metazoa and Choanoflagellata, the protozoan group most closely related to animals. These results show that this mode of regulation, characterized by an E(CG)-bearing core-promoter, is specific to almost all of the known genes involved in ribosome biogenesis in these genomes. Interestingly, this holozoan RiBi promoter signature is absent in nematode genomes, which have not only secondarily lost Myc but are marked by invariant cell lineages typically producing small body plans of 1000 somatic cells. Furthermore, a detailed analysis of 10 fungal genomes shows that this holozoan signature in RiBi genes is not found in hemiascomycete fungi, which evolved their own unique regulatory signature for the RiBi regulon.

Conclusion: These results indicate that a Myc regulon, which is activated in proliferating cells during normal development as well as during tumor progression, has primordial roots in the evolution of an inducible growth regime in a protozoan ancestor of animals. Furthermore, by comparing divergent bHLH repertoires, we conclude that regulation by Myc but not by other bHLH genes is responsible for the evolutionary maintenance of E(CG) sites across the RiBi suite of genes.

Show MeSH
Related in: MedlinePlus