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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F20%3A00118601" target="_blank" >RIV/00216224:14110/20:00118601 - isvavai.cz</a>

Result on the web

<a href="https://link.springer.com/article/10.1007/s00018-019-03251-w" target="_blank" >https://link.springer.com/article/10.1007/s00018-019-03251-w</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00018-019-03251-w" target="_blank" >10.1007/s00018-019-03251-w</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/NV15-32935A" target="_blank" >NV15-32935A: Analysis of tumour-reactive gamma/delta T cells in patients with B-cell chronic lymphocytic leukaemia: a new approach to the cellular therapy</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cellular and molecular life sciences

ISSN

1420-682X

e-ISSN

1420-9071

Volume of the periodical

77

Issue of the periodical within the volume

9

Country of publishing house

CH - SWITZERLAND

Number of pages

18

Pages from-to

1793-1810

UT code for WoS article

000529536500008

EID of the result in the Scopus database

2-s2.0-85084102609