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Nat Genet. 2018 Mar;50(3):329-332. doi: 10.1038/s41588-018-0042-y. Epub 2018 Jan 29.

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

Author information

1
MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh, UK.
2
MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh, UK.
3
Department of Biochemistry, Oxford University, Oxford, UK.
4
Cancer Genetics Clinic, Institute of Oncology, Ljubljana, Slovenia.
5
Department of Medical Genetics, Belfast City Hospital, Belfast, UK.
6
North West Thames Regional Genetics Service, London North West Healthcare NHS Trust, Harrow, UK.
7
South East Scotland Regional Genetics Services, Western General Hospital, Edinburgh, UK.
8
Department of Medical Genetics, Ashgrove House, Foresterhill, Aberdeen, UK.
9
East Anglian Medical Genetics Service, Clinical Genetics, Addenbrooke's Treatment Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
10
MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh, UK. wendy.bickmore@igmm.ed.ac.uk.
11
MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh, UK. pmadap@essex.ac.uk.
12
School of Biological Sciences, University of Essex, Colchester, UK. pmadap@essex.ac.uk.
13
MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh, UK. david.fitzpatrick@ed.ac.uk.

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.

PMID:
29379197
PMCID:
PMC6469577
DOI:
10.1038/s41588-018-0042-y
[Indexed for MEDLINE]
Free PMC Article

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