TY  - JOUR
A1  - Sakamak, Jun-ichi
A1  - Wilkinson, Simon
A1  - Hahn, Marcel
A1  - Tasdemir, Nilgun
A1  - O’Prey, Jim
A1  - Clark, William
A1  - Hedley, Ann
A1  - Nixon, Colin
A1  - Long, Jaclyn S.
A1  - New, Maria
A1  - Acker, Tim van
A1  - Tooze, Sharon A.
A1  - Lowe, Scott W.
A1  - Đikić, Ivan
A1  - Ryan, Kevin M.
T1  - Bromodomain protein BRD4 is a transcriptional repressor of autophagy and lysosomal function
T2  - Molecular cell
N2  - Autophagy is a membrane-trafficking process that directs degradation of cytoplasmic material in lysosomes. The process promotes cellular fidelity, and while the core machinery of autophagy is known, the mechanisms that promote and sustain autophagy are less well defined. Here we report that the epigenetic reader BRD4 and the methyltransferase G9a repress a TFEB/TFE3/MITF-independent transcriptional program that promotes autophagy and lysosome biogenesis. We show that BRD4 knockdown induces autophagy in vitro and in vivo in response to some, but not all, situations. In the case of starvation, a signaling cascade involving AMPK and histone deacetylase SIRT1 displaces chromatin-bound BRD4, instigating autophagy gene activation and cell survival. Importantly, this program is directed independently and also reciprocally to the growth-promoting properties of BRD4 and is potently repressed by BRD4-NUT, a driver of NUT midline carcinoma. These findings therefore identify a distinct and selective mechanism of autophagy regulation.
KW  - AMPK
KW  - BRD4
KW  - BRD4-NUT
KW  - G9a/EHMT2/KMT1C
KW  - SIRT1
KW  - autophagy
KW  - hMOF/KAT8
KW  - lysosomes
KW  - selective autophagy
KW  - transcriptional regulation of autophagy
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/43911
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-439119
SN  - 1097-4164
SN  - 1097-2765
N1  - This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
VL  - 66
IS  - 4, e9
SP  - 517
EP  - 532
PB  - Cell Press ; Elsevier
CY  - [Cambridge, Mass.] ; New York, NY
ER  -