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Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi.

Medina EM, Turner JJ, Gordân R, Skotheim JM, Buchler NE - Elife (2016)

Bottom Line: Cell cycle evolution in the fungal ancestor then proceeded through a hybrid network containing both SBF and its ancestral animal counterpart E2F, which is still maintained in many basal fungi.We hypothesize that a virally-derived SBF may have initially hijacked cell cycle control by activating transcription via the cis-regulatory elements targeted by the ancestral cell cycle regulator E2F, much like extant viral oncogenes.Consistent with this hypothesis, we show that SBF can regulate promoters with E2F binding sites in budding yeast.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Duke University, Durham, United States.

ABSTRACT
Although cell cycle control is an ancient, conserved, and essential process, some core animal and fungal cell cycle regulators share no more sequence identity than non-homologous proteins. Here, we show that evolution along the fungal lineage was punctuated by the early acquisition and entrainment of the SBF transcription factor through horizontal gene transfer. Cell cycle evolution in the fungal ancestor then proceeded through a hybrid network containing both SBF and its ancestral animal counterpart E2F, which is still maintained in many basal fungi. We hypothesize that a virally-derived SBF may have initially hijacked cell cycle control by activating transcription via the cis-regulatory elements targeted by the ancestral cell cycle regulator E2F, much like extant viral oncogenes. Consistent with this hypothesis, we show that SBF can regulate promoters with E2F binding sites in budding yeast.

No MeSH data available.


E2F and SBF show incongruences in sequence, structure, and mode of DNA binding.(A) Although both proteins share a winged helix-turn-helix (wHTH) domain, the E2F/DP and SBF/MBF superfamilies do not exhibit significant sequence identity or structural similarity to suggest a common recent evolutionary origin according to CATH or SCOP databases. Furthermore, each wHTH has a different mechanism of interaction with DNA: the arginine and tyrosine side-chains of recognition helix-3 of E2F (E2F4 from Homo sapiens [Zheng et al., 1999]) interact with specific CG nucleotides, where as the glutamine side-chains of the 'wing' of SBF/MBF (PCG2 from Magnaporthe oryzae [Liu et al., 2015]) interact with specific CG nucleotides. (B) Sequence alignment of the DNA binding domain of representative eukaryotic E2F/DP (left) and fungal SBF/MBF (right). The corresponding secondary structure is above the sequence alignment. Evolutionary conserved residues of sequence aligned DNA binding domains are highlighted in black. Bold sequence names correspond to E2F/DP and SBF/MBF sequences from basal fungi. Colored sequence names correspond to sequences of the structures shown in panel A. PDB IDs for the structures used are shown in parentheses. W = wing; T= turn.DOI:http://dx.doi.org/10.7554/eLife.09492.025
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fig5: E2F and SBF show incongruences in sequence, structure, and mode of DNA binding.(A) Although both proteins share a winged helix-turn-helix (wHTH) domain, the E2F/DP and SBF/MBF superfamilies do not exhibit significant sequence identity or structural similarity to suggest a common recent evolutionary origin according to CATH or SCOP databases. Furthermore, each wHTH has a different mechanism of interaction with DNA: the arginine and tyrosine side-chains of recognition helix-3 of E2F (E2F4 from Homo sapiens [Zheng et al., 1999]) interact with specific CG nucleotides, where as the glutamine side-chains of the 'wing' of SBF/MBF (PCG2 from Magnaporthe oryzae [Liu et al., 2015]) interact with specific CG nucleotides. (B) Sequence alignment of the DNA binding domain of representative eukaryotic E2F/DP (left) and fungal SBF/MBF (right). The corresponding secondary structure is above the sequence alignment. Evolutionary conserved residues of sequence aligned DNA binding domains are highlighted in black. Bold sequence names correspond to E2F/DP and SBF/MBF sequences from basal fungi. Colored sequence names correspond to sequences of the structures shown in panel A. PDB IDs for the structures used are shown in parentheses. W = wing; T= turn.DOI:http://dx.doi.org/10.7554/eLife.09492.025

Mentions: Many wHTH transcription factors, including the E2F/DP family, have a ‘recognition helix’ that interacts with the major or minor grooves of the DNA. The E2F/DP family has an RRXYD DNA-recognition motif in its helix that is invariant within the E2F/DP family and is responsible for interacting with the conserved, core GCGC motif (Zheng et al., 1999) (see Figure 5A: red structure). The RRXYD recognition motif is strikingly conserved in E2F/DP across all eukaryotes, including the E2F/DP proteins uncovered in basal fungi (Figure 5B, left). The first solved SBF/MBF crystal structure, Mbp1 from S. cerevisiae in the absence of DNA, originally suggested that Mbp1 recognizes its MCB (Mlu I cell cycle box, ACGCGT) binding site via a recognition helix (Taylor et al., 1997; Xu et al., 1997). However, a recent crystal structure of PCG2, an SBF/MBF homolog in the rice blast fungus Magnaporthe oryzae, in complex with its MCB binding site does not support this proposed mode of DNA binding (Liu et al., 2015). In striking contrast to many wHTH structures, in which the recognition helix is the mediator of DNA binding specificity, the wing of PCG2 binds to the minor groove to recognize the MCB binding site. The two glutamines in the wing (Q82, Q89) are the key elements that recognize the core MCB binding motif CGCG (Figure 5A, blue structure). Family-specific conservation in the DNA-binding domain is observed for all members of the SBF family, including basal fungal sequences (Figure 5B, right). In summary, the incongruences in sequence, structure, and mode of DNA-interaction between E2F/DP and SBF/MBF families strongly suggest that SBF is not derived from E2F.10.7554/eLife.09492.025Figure 5.E2F and SBF show incongruences in sequence, structure, and mode of DNA binding.


Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi.

Medina EM, Turner JJ, Gordân R, Skotheim JM, Buchler NE - Elife (2016)

E2F and SBF show incongruences in sequence, structure, and mode of DNA binding.(A) Although both proteins share a winged helix-turn-helix (wHTH) domain, the E2F/DP and SBF/MBF superfamilies do not exhibit significant sequence identity or structural similarity to suggest a common recent evolutionary origin according to CATH or SCOP databases. Furthermore, each wHTH has a different mechanism of interaction with DNA: the arginine and tyrosine side-chains of recognition helix-3 of E2F (E2F4 from Homo sapiens [Zheng et al., 1999]) interact with specific CG nucleotides, where as the glutamine side-chains of the 'wing' of SBF/MBF (PCG2 from Magnaporthe oryzae [Liu et al., 2015]) interact with specific CG nucleotides. (B) Sequence alignment of the DNA binding domain of representative eukaryotic E2F/DP (left) and fungal SBF/MBF (right). The corresponding secondary structure is above the sequence alignment. Evolutionary conserved residues of sequence aligned DNA binding domains are highlighted in black. Bold sequence names correspond to E2F/DP and SBF/MBF sequences from basal fungi. Colored sequence names correspond to sequences of the structures shown in panel A. PDB IDs for the structures used are shown in parentheses. W = wing; T= turn.DOI:http://dx.doi.org/10.7554/eLife.09492.025
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Related In: Results  -  Collection

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fig5: E2F and SBF show incongruences in sequence, structure, and mode of DNA binding.(A) Although both proteins share a winged helix-turn-helix (wHTH) domain, the E2F/DP and SBF/MBF superfamilies do not exhibit significant sequence identity or structural similarity to suggest a common recent evolutionary origin according to CATH or SCOP databases. Furthermore, each wHTH has a different mechanism of interaction with DNA: the arginine and tyrosine side-chains of recognition helix-3 of E2F (E2F4 from Homo sapiens [Zheng et al., 1999]) interact with specific CG nucleotides, where as the glutamine side-chains of the 'wing' of SBF/MBF (PCG2 from Magnaporthe oryzae [Liu et al., 2015]) interact with specific CG nucleotides. (B) Sequence alignment of the DNA binding domain of representative eukaryotic E2F/DP (left) and fungal SBF/MBF (right). The corresponding secondary structure is above the sequence alignment. Evolutionary conserved residues of sequence aligned DNA binding domains are highlighted in black. Bold sequence names correspond to E2F/DP and SBF/MBF sequences from basal fungi. Colored sequence names correspond to sequences of the structures shown in panel A. PDB IDs for the structures used are shown in parentheses. W = wing; T= turn.DOI:http://dx.doi.org/10.7554/eLife.09492.025
Mentions: Many wHTH transcription factors, including the E2F/DP family, have a ‘recognition helix’ that interacts with the major or minor grooves of the DNA. The E2F/DP family has an RRXYD DNA-recognition motif in its helix that is invariant within the E2F/DP family and is responsible for interacting with the conserved, core GCGC motif (Zheng et al., 1999) (see Figure 5A: red structure). The RRXYD recognition motif is strikingly conserved in E2F/DP across all eukaryotes, including the E2F/DP proteins uncovered in basal fungi (Figure 5B, left). The first solved SBF/MBF crystal structure, Mbp1 from S. cerevisiae in the absence of DNA, originally suggested that Mbp1 recognizes its MCB (Mlu I cell cycle box, ACGCGT) binding site via a recognition helix (Taylor et al., 1997; Xu et al., 1997). However, a recent crystal structure of PCG2, an SBF/MBF homolog in the rice blast fungus Magnaporthe oryzae, in complex with its MCB binding site does not support this proposed mode of DNA binding (Liu et al., 2015). In striking contrast to many wHTH structures, in which the recognition helix is the mediator of DNA binding specificity, the wing of PCG2 binds to the minor groove to recognize the MCB binding site. The two glutamines in the wing (Q82, Q89) are the key elements that recognize the core MCB binding motif CGCG (Figure 5A, blue structure). Family-specific conservation in the DNA-binding domain is observed for all members of the SBF family, including basal fungal sequences (Figure 5B, right). In summary, the incongruences in sequence, structure, and mode of DNA-interaction between E2F/DP and SBF/MBF families strongly suggest that SBF is not derived from E2F.10.7554/eLife.09492.025Figure 5.E2F and SBF show incongruences in sequence, structure, and mode of DNA binding.

Bottom Line: Cell cycle evolution in the fungal ancestor then proceeded through a hybrid network containing both SBF and its ancestral animal counterpart E2F, which is still maintained in many basal fungi.We hypothesize that a virally-derived SBF may have initially hijacked cell cycle control by activating transcription via the cis-regulatory elements targeted by the ancestral cell cycle regulator E2F, much like extant viral oncogenes.Consistent with this hypothesis, we show that SBF can regulate promoters with E2F binding sites in budding yeast.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Duke University, Durham, United States.

ABSTRACT
Although cell cycle control is an ancient, conserved, and essential process, some core animal and fungal cell cycle regulators share no more sequence identity than non-homologous proteins. Here, we show that evolution along the fungal lineage was punctuated by the early acquisition and entrainment of the SBF transcription factor through horizontal gene transfer. Cell cycle evolution in the fungal ancestor then proceeded through a hybrid network containing both SBF and its ancestral animal counterpart E2F, which is still maintained in many basal fungi. We hypothesize that a virally-derived SBF may have initially hijacked cell cycle control by activating transcription via the cis-regulatory elements targeted by the ancestral cell cycle regulator E2F, much like extant viral oncogenes. Consistent with this hypothesis, we show that SBF can regulate promoters with E2F binding sites in budding yeast.

No MeSH data available.