BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange–like syndrome

Olley, G. et al. (2018) BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange–like syndrome. Nature Genetics, 50(3), pp. 329-332. (doi: 10.1038/s41588-018-0042-y) (PMID:29379197)

Abstract

We found that the clinical phenotype associated with BRD4 haploinsufficiency overlapped with that of Cornelia de Lange syndrome (CdLS), which is most often caused by mutation of NIPBL. More typical CdLS was observed with a de novo BRD4 missense variant, which retained the ability to coimmunoprecipitate with NIPBL, but bound poorly to acetylated histones. BRD4 and NIPBL displayed correlated binding at super-enhancers and appeared to co-regulate developmental gene expression.

• Item Type: Articles
• Additional Information: G.O., M.A., H.B., W.A.B., M.M.P. and D.R.F. were funded by the MRC University Unit award to the University of Edinburgh for the MRC Human Genetics Unit. The work of A.v.K. was supported by Carnegie Trust Research Incentive Grant 70382. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant WT098051).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Tobias, Professor Edward
• Authors: Olley, G., Ansari, M., Bengani, H., Grimes, G. R., Rhodes, J., von Kriegsheim, A., Blatnik, A., Stewart, F. J., Wakeling, E., Carroll, N., Ross, A., Park, S.-M., Deciphering Developmental Disorders Study, , Bickmore, W. A., Pradeepa, M. M., and FitzPatrick, D. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Nature Genetics
• Publisher: Nature Research
• ISSN: 1061-4036
• ISSN (Online): 1546-1718
• Published Online: 29 January 2018
• Copyright Holders: Copyright © 2018 Nature America Inc., part of Springer Nature
• First Published: First published in Nature Research 49:249-255
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher