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.