PuSH - Publication Server of Helmholtz Zentrum München: BRD4 promotes p63 and GRHL3 expression downstream of FOXO in mammary epithelial cells.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

EVA: Electronic Publishing

New EVA Application

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Nagarajan, S.* ; Bedi, U.* ; Budida, A.* ; Hamdan, F.H.* ; Mishra, V.K.* ; Najafova, Z.* ; Xie, W.* ; Alawi, M.* ; Indenbirken, D.* ; Knapp, S.* ; Chiang, C.M.* ; Grundhoff, A.* ; Kari, V.* ; Scheel, C. ; Wegwitz, F.* ; Johnsen, S.A.*

BRD4 promotes p63 and GRHL3 expression downstream of FOXO in mammary epithelial cells.

Nucleic Acids Res. 45, 3130-3145 (2016)

Publ. Version/Full Text

Research data

DOI

PMC

	Open Access Gold

Abstract
Metrics
Extra information

Bromodomain-containing protein 4 (BRD4) is amember of the bromo-and extraterminal (BET) domaincontaining family of epigenetic readers which is under intensive investigation as a target for anti-tumor therapy. BRD4 plays a central role in promoting the expression of select subsets of genes including many driven by oncogenic transcription factors and signaling pathways. However, the role of BRD4 and the effects of BET inhibitors in non-transformed cells remain mostly unclear. We demonstrate that BRD4 is required for the maintenance of a basal epithelial phenotype by regulating the expression of epithelialspecific genes including TP63 and Grainy Head-like transcription factor-3 (GRHL3) in non-transformed basal-like mammary epithelial cells. Moreover, BRD4 occupancy correlates with enhancer activity and enhancer RNA (eRNA) transcription. Motif analyses of cell context-specific BRD4-enriched regions predicted the involvement of FOXOtranscription factors. Consistently, activation of FOXO1 function via inhibition of EGFR-AKT signaling promoted the expression of TP63 and GRHL3. Moreover, activation of Src kinase signaling and FOXO1 inhibition decreased the expression of FOXO/BRD4 target genes. Together, our findings support a function for BRD4 in promoting basal mammary cell epithelial differentiation, at least in part, by regulating FOXO factor function on enhancers to activate TP63 and GRHL3 expression.

Impact Factor

Scopus SNIP

Web of Science
Times Cited

Scopus
Cited By

Altmetric

9.202

2.515