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The transcription factors Tec1 and Ste12 interact with coregulators Msa1 and Msa2 to activate adhesion and multicellular development.

ABSTRACT: In Saccharomyces cerevisiae and related yeast species, the TEA transcription factor Tec1, together with a second transcription factor, Ste12, controls development, including cell adhesion and filament formation. Tec1-Ste12 complexes control target genes through Tec1 binding sites (TEA consensus sequences [TCSs]) that can be further combined with Ste12 binding sites (pheromone response elements [PREs]) for cooperative DNA binding. The activity of Tec1-Ste12 complexes is known to be under negative control of the Dig1 and Dig2 (Dig1/2) transcriptional corepressors that confer regulation by upstream signaling pathways. Here, we found that Tec1 and Ste12 can associate with the transcriptional coregulators Msa1 and Msa2 (Msa1/2), which were previously found to associate with the cell cycle transcription factor complexes SBF (Swi4/Swi6 cell cycle box binding factor) and MBF (Mbp1/Swi6 cell cycle box binding factor) to control G1-specific transcription. We further show that Tec1-Ste12-Msa1/2 complexes (i) do not contain Swi4 or Mbp1, (ii) assemble at single TCSs or combined TCS-PREs in vitro, and (iii) coregulate genes involved in adhesive and filamentous growth by direct promoter binding in vivo. Finally, we found that, in contrast to Dig proteins, Msa1/2 seem to act as coactivators that enhance the transcriptional activity of Tec1-Ste12. Taken together, our findings add an additional layer of complexity to our understanding of the control mechanisms exerted by the evolutionarily conserved TEA domain and Ste12-like transcription factors.

SUBMITTER: van der Felden J

PROVIDER: S-EPMC4054286 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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The transcription factors Tec1 and Ste12 interact with coregulators Msa1 and Msa2 to activate adhesion and multicellular development.

van der Felden Julia J Weisser Sarah S Brückner Stefan S Lenz Peter P Mösch Hans-Ulrich HU

Molecular and cellular biology 20140414 12

In Saccharomyces cerevisiae and related yeast species, the TEA transcription factor Tec1, together with a second transcription factor, Ste12, controls development, including cell adhesion and filament formation. Tec1-Ste12 complexes control target genes through Tec1 binding sites (TEA consensus sequences [TCSs]) that can be further combined with Ste12 binding sites (pheromone response elements [PREs]) for cooperative DNA binding. The activity of Tec1-Ste12 complexes is known to be under negative ...[more]

PMID: 24732795

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Project description:Melanocytes, the pigment-producing cells, arise from multipotent neural crest (NC) cells during embryogenesis. Many genes required for melanocyte development were identified using mouse pigmentation mutants. The variable spotting mouse pigmentation mutant arose spontaneously at the Jackson Laboratory. We identified a G-to-A nucleotide transition in exon 3 of the Ets1 gene in variable spotting, which results in a missense G102E mutation. Homozygous variable spotting mice exhibit sporadic white spotting. Similarly, mice carrying a targeted deletion of Ets1 exhibit hypopigmentation; nevertheless, the function of Ets1 in melanocyte development is unknown. The transcription factor Ets1 is widely expressed in developing organs and tissues, including the NC. In the chick, Ets1 is required for the expression of Sox10, a transcription factor critical for the development of various NC derivatives, including melanocytes. We show that Ets1 is required early for murine NC cell and melanocyte precursor survival in vivo. Given the importance of Ets1 for Sox10 expression in the chick, we investigated a potential genetic interaction between these genes by comparing the hypopigmentation phenotypes of single and double heterozygous mice. The incidence of hypopigmentation in double heterozygotes was significantly greater than in single heterozygotes. The area of hypopigmentation in double heterozygotes was significantly larger than would be expected from the addition of the areas of hypopigmentation of single heterozygotes, suggesting that Ets1 and Sox10 interact synergistically in melanocyte development. Since Sox10 is also essential for enteric ganglia development, we examined the distal colons of Ets1 null mutants and found a significant decrease in enteric innervation, which was exacerbated by Sox10 heterozygosity. At the molecular level, Ets1 was found to activate an enhancer critical for Sox10 expression in NC-derived structures. Furthermore, enhancer activation was significantly inhibited by the variable spotting mutation. Together, these results suggest that Ets1 and Sox10 interact to promote proper melanocyte and enteric ganglia development from the NC.

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The transcription factors Tec1 and Ste12 interact with coregulators Msa1 and Msa2 to activate adhesion and multicellular development.

Publications

The transcription factors Tec1 and Ste12 interact with coregulators Msa1 and Msa2 to activate adhesion and multicellular development.

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