The nuclear localization pattern and interaction partners of GTF2IRD1 demonstrate a role in chromatin regulation

Carmona-Mora, Paulina, Widagdo, Jocelyn, Tomasetig, Florence, Canales, Cesar P, Cha, Yeojoon, Lee, Wei, Alshawaf, Abdullah, Dottori, Mirella, Whan, Renee M, Hardeman, Edna C and Palmer, Stephen J (2015) The nuclear localization pattern and interaction partners of GTF2IRD1 demonstrate a role in chromatin regulation. Human Genetics, 134 10: 1099-1115. doi:10.1007/s00439-015-1591-0

Author Carmona-Mora, Paulina
Widagdo, Jocelyn
Tomasetig, Florence
Canales, Cesar P
Cha, Yeojoon
Lee, Wei
Alshawaf, Abdullah
Dottori, Mirella
Whan, Renee M
Hardeman, Edna C
Palmer, Stephen J
Title The nuclear localization pattern and interaction partners of GTF2IRD1 demonstrate a role in chromatin regulation
Journal name Human Genetics   Check publisher's open access policy
ISSN 1432-1203
Publication date 2015-08-15
Year available 2015
Sub-type Article (original research)
DOI 10.1007/s00439-015-1591-0
Open Access Status Not Open Access
Volume 134
Issue 10
Start page 1099
End page 1115
Total pages 17
Place of publication Heidelberg, Germany
Publisher Springer
Collection year 2016
Language eng
Formatted abstract
GTF2IRD1 is one of the three members of the GTF2I gene family, clustered on chromosome 7 within a 1.8 Mb region that is prone to duplications and deletions in humans. Hemizygous deletions cause Williams–Beuren syndrome (WBS) and duplications cause WBS duplication syndrome. These copy number variations disturb a variety of developmental systems and neurological functions. Human mapping data and analyses of knockout mice show that GTF2IRD1 and GTF2I underpin the craniofacial abnormalities, mental retardation, visuospatial deficits and hypersociability of WBS. However, the cellular role of the GTF2IRD1 protein is poorly understood due to its very low abundance and a paucity of reagents. Here, for the first time, we show that endogenous GTF2IRD1 has a punctate pattern in the nuclei of cultured human cell lines and neurons. To probe the functional relationships of GTF2IRD1 in an unbiased manner, yeast two-hybrid libraries were screened, isolating 38 novel interaction partners, which were validated in mammalian cell lines. These relationships illustrate GTF2IRD1 function, as the isolated partners are mostly involved in chromatin modification and transcriptional regulation, whilst others indicate an unexpected role in connection with the primary cilium. Mapping of the sites of protein interaction also indicates key features regarding the evolution of the GTF2IRD1 protein. These data provide a visual and molecular basis for GTF2IRD1 nuclear function that will lead to an understanding of its role in brain, behaviour and human disease.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
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Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
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