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@article{1656936, author = {Piskáček, Martin and Havelka, Marek and Jendruchová, Kristína and Knight, Andrea and Keegan, Liam}, article_location = {BASEL}, article_number = {9}, doi = {http://dx.doi.org/10.1007/s00018-019-03251-w}, keywords = {KLF; WT1; Gal4; Met4; Gcn4; E2A; MLL; p53; MED15; TAF9; CBP; KIX}, language = {eng}, issn = {1420-682X}, journal = {Cellular and molecular life sciences}, title = {The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with valines and intron reservoirs}, url = {https://link.springer.com/article/10.1007/s00018-019-03251-w}, volume = {77}, year = {2020} }
TY - JOUR ID - 1656936 AU - Piskáček, Martin - Havelka, Marek - Jendruchová, Kristína - Knight, Andrea - Keegan, Liam PY - 2020 TI - The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with valines and intron reservoirs JF - Cellular and molecular life sciences VL - 77 IS - 9 SP - 1793-1810 EP - 1793-1810 PB - BIRKHAUSER VERLAG AG SN - 1420682X KW - KLF KW - WT1 KW - Gal4 KW - Met4 KW - Gcn4 KW - E2A KW - MLL KW - p53 KW - MED15 KW - TAF9 KW - CBP KW - KIX UR - https://link.springer.com/article/10.1007/s00018-019-03251-w L2 - https://link.springer.com/article/10.1007/s00018-019-03251-w N2 - The universal nine-amino-acid transactivation domains (9aaTADs) have been identified in numerous transcription activators. Here, we identified the conserved 9aaTAD motif in all nine members of the specificity protein (SP) family. Previously, the Sp1 transcription factor has been defined as a glutamine-rich activator. We showed by amino acid substitutions that the glutamine residues are completely dispensable for 9aaTAD function and are not conserved in the SP family. We described the origin and evolutionary history of 9aaTADs. The 9aaTADs of the ancestral Sp2 gene became inactivated in early chordates. We next discovered that an accumulation of valines in 9aaTADs inactivated their transactivation function and enabled their strict conservation during evolution. Subsequently, in chordates, Sp2 has duplicated and created new paralogs, Sp1, Sp3, and Sp4 (the SP1-4 clade). During chordate evolution, the dormancy of the Sp2 activation domain lasted over 100 million years. The dormant but still intact ancestral Sp2 activation domains allowed diversification of the SP1-4 clade into activators and repressors. By valine substitution in the 9aaTADs, Sp1 and Sp3 regained their original activator function found in ancestral lower metazoan sea sponges. Therefore, the vertebrate SP1-4 clade could include both repressors and activators. Furthermore, we identified secondary 9aaTADs in Sp2 introns present from fish to primates, including humans. In the gibbon genome, introns containing 9aaTADs were used as exons, which turned the Sp2 gene into an activator. Similarly, we identified introns containing 9aaTADs used conditionally as exons in the (SP family-unrelated) transcription factor SREBP1, suggesting that the intron-9aaTAD reservoir is a general phenomenon. ER -
PISKÁČEK, Martin, Marek HAVELKA, Kristína JENDRUCHOVÁ, Andrea KNIGHT a Liam KEEGAN. The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with valines and intron reservoirs. \textit{Cellular and molecular life sciences}. BASEL: BIRKHAUSER VERLAG AG, 2020, roč.~77, č.~9, s.~1793-1810. ISSN~1420-682X. Dostupné z: https://dx.doi.org/10.1007/s00018-019-03251-w.
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