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Variable Glutamine-Rich Repeats Modulate Transcription Factor Activity.

Gemayel R, Chavali S, Pougach K, Legendre M, Zhu B, Boeynaems S, van der Zande E, Gevaert K, Rousseau F, Schymkowitz J, Babu MM, Verstrepen KJ - Mol. Cell (2015)

Bottom Line: Incremental changes in the number of repeats in the yeast transcriptional regulator Ssn6 (Cyc8) result in systematic, repeat-length-dependent variation in expression of target genes that result in direct phenotypic changes.Quantitative proteomic analysis reveals that the Ssn6 repeats affect its solubility and interactions with Tup1 and other regulators.Thus, Q-rich repeats are dynamic functional domains that modulate a regulator's innate function, with the inherent risk of pathogenic repeat expansions.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Systems Biology, VIB, Gaston Geenslaan 1, 3001 Heverlee, Belgium; Laboratory of Genetics and Genomics, Centre of Microbial and Plant Genetics (CMPG), Department M2S, KU Leuven, Gaston Geenslaan 1, 3001 Heverlee, Belgium.

No MeSH data available.


Related in: MedlinePlus

The Q-Rich Repeats in Saccharomyces cerevisiae Transcriptional Regulator Ssn6 Show Variability between Natural Yeast Strains(A) Schematic representation of the Ssn6 protein showing the two repeat regions. TR1 denotes the N-terminal polyQ (residues 15 to 30), and TR2 denotes the central Q-rich repeat (residues 493 to 587). The natural range of repeat number variation is indicated underneath each repeat region. See also Figure S3.(B) The TR1 region of SSN6 from various S. cerevisiae strains was amplified by PCR.(C) Amplification of the SSN6 TR2 region from various S. cerevisiae strains. The asterisks denote genetically close strains YPS606 (∗) and YPS128 (∗∗) with different TR2 sizes. See also Table S3.(D) TR sizes in representative SSN6 variants constructed for this study. Total repeat numbers are given. The asterisk indicates the repeat number in the WT strain. Repeat numbers falling within the range observed in natural strains (C) are indicated.
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fig2: The Q-Rich Repeats in Saccharomyces cerevisiae Transcriptional Regulator Ssn6 Show Variability between Natural Yeast Strains(A) Schematic representation of the Ssn6 protein showing the two repeat regions. TR1 denotes the N-terminal polyQ (residues 15 to 30), and TR2 denotes the central Q-rich repeat (residues 493 to 587). The natural range of repeat number variation is indicated underneath each repeat region. See also Figure S3.(B) The TR1 region of SSN6 from various S. cerevisiae strains was amplified by PCR.(C) Amplification of the SSN6 TR2 region from various S. cerevisiae strains. The asterisks denote genetically close strains YPS606 (∗) and YPS128 (∗∗) with different TR2 sizes. See also Table S3.(D) TR sizes in representative SSN6 variants constructed for this study. Total repeat numbers are given. The asterisk indicates the repeat number in the WT strain. Repeat numbers falling within the range observed in natural strains (C) are indicated.

Mentions: To assess whether the variability in Q-rich repeats within transcriptional regulators directly influences the expression of downstream targets, we chose the S. cerevisiae transcriptional regulator Ssn6 (Cyc8) (Chen et al., 2013; Tzamarias and Struhl, 1994; Wong and Struhl, 2011). Ssn6 is a TF that controls a large number of targets that show high expression variability (Figure 1E). The SSN6 coding sequence comprises two Q-rich repeat regions: a first polyQ stretch (residues 15–30), henceforth referred to as Tandem Repeat 1 (TR1), and a second Q-rich region, comprised of an array of QA repeats directly followed by a polyQ stretch (residues 493–587), referred to as TR2 (Figure 2A).


Variable Glutamine-Rich Repeats Modulate Transcription Factor Activity.

Gemayel R, Chavali S, Pougach K, Legendre M, Zhu B, Boeynaems S, van der Zande E, Gevaert K, Rousseau F, Schymkowitz J, Babu MM, Verstrepen KJ - Mol. Cell (2015)

The Q-Rich Repeats in Saccharomyces cerevisiae Transcriptional Regulator Ssn6 Show Variability between Natural Yeast Strains(A) Schematic representation of the Ssn6 protein showing the two repeat regions. TR1 denotes the N-terminal polyQ (residues 15 to 30), and TR2 denotes the central Q-rich repeat (residues 493 to 587). The natural range of repeat number variation is indicated underneath each repeat region. See also Figure S3.(B) The TR1 region of SSN6 from various S. cerevisiae strains was amplified by PCR.(C) Amplification of the SSN6 TR2 region from various S. cerevisiae strains. The asterisks denote genetically close strains YPS606 (∗) and YPS128 (∗∗) with different TR2 sizes. See also Table S3.(D) TR sizes in representative SSN6 variants constructed for this study. Total repeat numbers are given. The asterisk indicates the repeat number in the WT strain. Repeat numbers falling within the range observed in natural strains (C) are indicated.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4543046&req=5

fig2: The Q-Rich Repeats in Saccharomyces cerevisiae Transcriptional Regulator Ssn6 Show Variability between Natural Yeast Strains(A) Schematic representation of the Ssn6 protein showing the two repeat regions. TR1 denotes the N-terminal polyQ (residues 15 to 30), and TR2 denotes the central Q-rich repeat (residues 493 to 587). The natural range of repeat number variation is indicated underneath each repeat region. See also Figure S3.(B) The TR1 region of SSN6 from various S. cerevisiae strains was amplified by PCR.(C) Amplification of the SSN6 TR2 region from various S. cerevisiae strains. The asterisks denote genetically close strains YPS606 (∗) and YPS128 (∗∗) with different TR2 sizes. See also Table S3.(D) TR sizes in representative SSN6 variants constructed for this study. Total repeat numbers are given. The asterisk indicates the repeat number in the WT strain. Repeat numbers falling within the range observed in natural strains (C) are indicated.
Mentions: To assess whether the variability in Q-rich repeats within transcriptional regulators directly influences the expression of downstream targets, we chose the S. cerevisiae transcriptional regulator Ssn6 (Cyc8) (Chen et al., 2013; Tzamarias and Struhl, 1994; Wong and Struhl, 2011). Ssn6 is a TF that controls a large number of targets that show high expression variability (Figure 1E). The SSN6 coding sequence comprises two Q-rich repeat regions: a first polyQ stretch (residues 15–30), henceforth referred to as Tandem Repeat 1 (TR1), and a second Q-rich region, comprised of an array of QA repeats directly followed by a polyQ stretch (residues 493–587), referred to as TR2 (Figure 2A).

Bottom Line: Incremental changes in the number of repeats in the yeast transcriptional regulator Ssn6 (Cyc8) result in systematic, repeat-length-dependent variation in expression of target genes that result in direct phenotypic changes.Quantitative proteomic analysis reveals that the Ssn6 repeats affect its solubility and interactions with Tup1 and other regulators.Thus, Q-rich repeats are dynamic functional domains that modulate a regulator's innate function, with the inherent risk of pathogenic repeat expansions.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Systems Biology, VIB, Gaston Geenslaan 1, 3001 Heverlee, Belgium; Laboratory of Genetics and Genomics, Centre of Microbial and Plant Genetics (CMPG), Department M2S, KU Leuven, Gaston Geenslaan 1, 3001 Heverlee, Belgium.

No MeSH data available.


Related in: MedlinePlus