J 2020

The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with valines and intron reservoirs

PISKÁČEK, Martin, Marek HAVELKA, Kristína JENDRUCHOVÁ, Andrea KNIGHT, Liam KEEGAN et. al.

Basic information

Original name

The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with valines and intron reservoirs

Authors

PISKÁČEK, Martin (40 Austria, guarantor, belonging to the institution), Marek HAVELKA (203 Czech Republic, belonging to the institution), Kristína JENDRUCHOVÁ (703 Slovakia, belonging to the institution), Andrea KNIGHT (203 Czech Republic, belonging to the institution) and Liam KEEGAN (372 Ireland, belonging to the institution)

Edition

Cellular and molecular life sciences, BASEL, BIRKHAUSER VERLAG AG, 2020, 1420-682X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 9.261

RIV identification code

RIV/00216224:14110/20:00118601

Organization unit

Faculty of Medicine

UT WoS

000529536500008

Keywords in English

KLF; WT1; Gal4; Met4; Gcn4; E2A; MLL; p53; MED15; TAF9; CBP; KIX

Tags

International impact, Reviewed
Změněno: 20/5/2020 13:33, Mgr. Tereza Miškechová

Abstract

V originále

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.

Links

NV15-32935A, research and development project
Name: Analýza gamma-delta T lymfocytů reaktivních na nádorové buňky u pacientů s B-buněčnou chronickou lymfocytární leukémií: nový přístup k buněčné terapii