Limits...
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.

Show MeSH

Related in: MedlinePlus

Holozoan RiBi promoters are enriched in E(CG) sites. The percentage of E(CG)-bearing promoters in RiBi genes is two to four fold higher in D. melanogaster (Dm), H. sapiens (Hs), N. vectensis (Nv), and M. brevicollis (Mb) relative to negative control sequences composed of promoter regions of downstream conserved genes (C1), the 3' regions of RiBi genes (C2), or the promoters of genes with GO mitochondrial classification (CM). This difference between RiBi and C1, C2, or CM is lacking in outgroup genomes such as S. cerevisiae (Sc), which lack Myc, as well as in the nematode genome of C. elegans (Ce), which has secondarily lost Myc (Fig. 3). Inset depicts phylogenetic relationships among these organisms.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2570694&req=5

Figure 2: Holozoan RiBi promoters are enriched in E(CG) sites. The percentage of E(CG)-bearing promoters in RiBi genes is two to four fold higher in D. melanogaster (Dm), H. sapiens (Hs), N. vectensis (Nv), and M. brevicollis (Mb) relative to negative control sequences composed of promoter regions of downstream conserved genes (C1), the 3' regions of RiBi genes (C2), or the promoters of genes with GO mitochondrial classification (CM). This difference between RiBi and C1, C2, or CM is lacking in outgroup genomes such as S. cerevisiae (Sc), which lack Myc, as well as in the nematode genome of C. elegans (Ce), which has secondarily lost Myc (Fig. 3). Inset depicts phylogenetic relationships among these organisms.

Mentions: To determine the evolutionary origins of the RiBi regulon, we first measured the conservation of E(CG) motifs in the RiBi genes of other bilaterian genomes, including humans and nematodes. Of the human RiBi genes, 77%, possess an E(CG) in a window ± 600 bp from the 5' annotated end, which is a significantly elevated compared to the ~20% background level in control promoters (Fig. 2; Table 1). In contrast with humans, there is no elevated level of E(CG) in RiBi genes in the nematode genome of C. elegans despite the conservation of such genes (Fig. 2). The presence of an E(CG)-RiBi signature in both a deuterostome (humans) and a protostome (flies) suggests that the absence in another protostome (nematodes) is a secondary loss.


Evolution of the holozoan ribosome biogenesis regulon.

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

Holozoan RiBi promoters are enriched in E(CG) sites. The percentage of E(CG)-bearing promoters in RiBi genes is two to four fold higher in D. melanogaster (Dm), H. sapiens (Hs), N. vectensis (Nv), and M. brevicollis (Mb) relative to negative control sequences composed of promoter regions of downstream conserved genes (C1), the 3' regions of RiBi genes (C2), or the promoters of genes with GO mitochondrial classification (CM). This difference between RiBi and C1, C2, or CM is lacking in outgroup genomes such as S. cerevisiae (Sc), which lack Myc, as well as in the nematode genome of C. elegans (Ce), which has secondarily lost Myc (Fig. 3). Inset depicts phylogenetic relationships among these organisms.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Holozoan RiBi promoters are enriched in E(CG) sites. The percentage of E(CG)-bearing promoters in RiBi genes is two to four fold higher in D. melanogaster (Dm), H. sapiens (Hs), N. vectensis (Nv), and M. brevicollis (Mb) relative to negative control sequences composed of promoter regions of downstream conserved genes (C1), the 3' regions of RiBi genes (C2), or the promoters of genes with GO mitochondrial classification (CM). This difference between RiBi and C1, C2, or CM is lacking in outgroup genomes such as S. cerevisiae (Sc), which lack Myc, as well as in the nematode genome of C. elegans (Ce), which has secondarily lost Myc (Fig. 3). Inset depicts phylogenetic relationships among these organisms.
Mentions: To determine the evolutionary origins of the RiBi regulon, we first measured the conservation of E(CG) motifs in the RiBi genes of other bilaterian genomes, including humans and nematodes. Of the human RiBi genes, 77%, possess an E(CG) in a window ± 600 bp from the 5' annotated end, which is a significantly elevated compared to the ~20% background level in control promoters (Fig. 2; Table 1). In contrast with humans, there is no elevated level of E(CG) in RiBi genes in the nematode genome of C. elegans despite the conservation of such genes (Fig. 2). The presence of an E(CG)-RiBi signature in both a deuterostome (humans) and a protostome (flies) suggests that the absence in another protostome (nematodes) is a secondary loss.

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