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Type: Journal article
Title: Protocadherin 19 (PCDH19) interacts with paraspeckle protein NONO to co-regulate gene expression with estrogen receptor alpha (ERα)
Other Titles: Protocadherin 19 (PCDH19) interacts with paraspeckle protein NONO to co-regulate gene expression with estrogen receptor alpha (ERalpha)
Author: Pham, D.
Tan, C.
Homan, C.
Kolc, K.L.
Corbett, M.
McAninch, D.
Fox, A.
Thomas, P.
Kumar, R.
Gecz, J.
Citation: Human Molecular Genetics, 2017; 26(11):2042-2052
Publisher: Oxford University Press
Issue Date: 2017
ISSN: 0964-6906
Statement of
Duyen H. Pham, Chuan C. Tan, Claire C. Homan, Kristy L. Kolc, Mark A. Corbett, Dale McAninch, Archa H. Fox, Paul Q. Thomas, Raman Kumar Jozef Gecz
Abstract: De novo and inherited mutations of X-chromosome cell adhesion molecule protocadherin 19 (PCDH19) cause frequent, highly variable epilepsy, autism, cognitive decline and behavioural problems syndrome. Intriguingly, hemizygous null males are not affected while heterozygous females are, contradicting established X-chromosome inheritance. The disease mechanism is not known. Cellular mosaicism is the likely driver. We have identified p54nrb/NONO, a multifunctional nuclear paraspeckle protein with known roles in nuclear hormone receptor gene regulation, as a PCDH19 protein interacting partner. Using breast cancer cells we show that PCDH19-NONO complex is a positive co-regulator of ERα-mediated gene expression. Expression of mutant PCDH19 affects at least a subset of known ERα-regulated genes. These data are consistent with our findings that genes regulated by nuclear hormone receptors and those involved in the metabolism of neurosteroids in particular are dysregulated in PCDH19-epilepsy girls and affected mosaic males. Overall we define and characterize a novel mechanism of gene regulation driven by PCDH19, which is mediated by paraspeckle constituent NONO and is ERα-dependent. This PCDH19-NONO-ERα axis is of relevance not only to PCDH19-epilepsy and its comorbidities but likely also to ERα and generally nuclear hormone receptor-associated cancers.
Keywords: Cell Line, Tumor
Breast Neoplasms
RNA-Binding Proteins
Nuclear Matrix-Associated Proteins
Estrogen Receptor alpha
Gene Expression
Gene Expression Regulation, Neoplastic
Octamer Transcription Factors
HEK293 Cells
Intellectual Disability
Rights: © The Author 2017. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact
DOI: 10.1093/hmg/ddx094
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