GTF2IRD2 from the Williams-Beuren critical region encodes a mobile-element-derived fusion protein that antagonizes the action of its related family members

Palmer, Stephen J., Taylor, Kylie M., Santucci, Nicole, Widagdo, Jocelyn, Chan, Yee-Ka Agnes, Yeo, Jen-Li, Adams, Merritt, Gunning, Peter W. and Hardeman, Edna C. (2012) GTF2IRD2 from the Williams-Beuren critical region encodes a mobile-element-derived fusion protein that antagonizes the action of its related family members. Journal of Cell Science, 125 21: 5040-5050. doi:10.1242/jcs.102798

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Author Palmer, Stephen J.
Taylor, Kylie M.
Santucci, Nicole
Widagdo, Jocelyn
Chan, Yee-Ka Agnes
Yeo, Jen-Li
Adams, Merritt
Gunning, Peter W.
Hardeman, Edna C.
Title GTF2IRD2 from the Williams-Beuren critical region encodes a mobile-element-derived fusion protein that antagonizes the action of its related family members
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 0021-9533
1477-9137
Publication date 2012
Year available 2012
Sub-type Article (original research)
DOI 10.1242/jcs.102798
Open Access Status File (Publisher version)
Volume 125
Issue 21
Start page 5040
End page 5050
Total pages 11
Place of publication Cambridge, United Kingdom
Publisher The Company of Biologists Ltd.
Collection year 2012
Language eng
Subject 1307 Cell Biology
Abstract GTF2IRD2 belongs to a family of transcriptional regulators (including TFII-I and GTF2IRD1) that are responsible for many of the key features of Williams-Beuren syndrome (WBS). Sequence evidence suggests that GTF2IRD2 arose in eutherian mammals by duplication and divergence from the gene encoding TFII-I. However, in GTF2IRD2, most of the C-terminal domain has been lost and replaced by the domesticated remnant of an in-frame hAT-transposon mobile element. In this first experimental analysis of function, we show that transgenic expression of each of the three family members in skeletal muscle causes significant fiber type shifts, but the GTF2IRD2 protein causes an extreme shift in the opposite direction to the two other family members. Mating of GTF2IRD1 and GTF2IRD2 mice restores the fiber type balance, indicating an antagonistic relationship between these two paralogs. In cells, GTF2IRD2 localizes to cytoplasmic microtubules and discrete speckles in the nuclear periphery. We show that it can interact directly with TFII-IΒ and GTF2IRD1, and upon co-transfection changes the normal distribution of these two proteins into a punctate nuclear pattern typical of GTF2IRD2. These data suggest that GTF2IRD2 has evolved as a regulator of GTF2IRD1 and TFII-I; inhibiting their function by direct interaction and sequestration into inactive nuclear zones.
Keyword Muscle
Nuclear speckles
Transgenic
Transposon
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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