Extended HSR/CARD domain mediates AIRE binding to DNA

Julia Maslovskaja; Mario Saare; Ingrid Liiv; Ana Rebane; Pärt Peterson

doi:10.1016/j.bbrc.2015.11.056

Extended HSR/CARD domain mediates AIRE binding to DNA

Biochem Biophys Res Commun. 2015 Dec 25;468(4):913-20. doi: 10.1016/j.bbrc.2015.11.056. Epub 2015 Nov 27.

Authors

Julia Maslovskaja¹, Mario Saare², Ingrid Liiv², Ana Rebane², Pärt Peterson²

Affiliations

¹ Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411, Estonia. Electronic address: [email protected].
² Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411, Estonia.

PMID: 26607109
DOI: 10.1016/j.bbrc.2015.11.056

Abstract

Autoimmune regulator (AIRE) activates the transcription of many genes in an unusual promiscuous and stochastic manner. The mechanism by which AIRE binds to the chromatin and DNA is not fully understood, and the regulatory elements that AIRE target genes possess are not delineated. In the current study, we demonstrate that AIRE activates the expression of transiently transfected luciferase reporters that lack defined promoter regions, as well as intron and poly(A) signal sequences. Our protein-DNA interaction experiments with mutated AIRE reveal that the intact homogeneously staining region/caspase recruitment domain (HSR/CARD) and amino acids R113 and K114 are key elements involved in AIRE binding to DNA.

Keywords: AIRE; APECED; DNA binding; Gene activation; HSR/CARD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AIRE Protein
Binding Sites
CARD Signaling Adaptor Proteins / chemistry*
CARD Signaling Adaptor Proteins / metabolism*
DNA / chemistry*
DNA / metabolism*
HEK293 Cells
Humans
Protein Binding
Structure-Activity Relationship
Transcription Factors / chemistry*
Transcription Factors / metabolism*

Substances

CARD Signaling Adaptor Proteins
Transcription Factors
DNA