PARty promoters: hormone-dependent gene regulation requires CDK2 activation of PARP1

Abstract

Eukaryotic cells have to overcome the complexity of chromatin organization in order to gain access to DNA to activate or repress transcription. The organization of chromatin itself acts as a physical restraint. Generally, in order to activate transcription, cells must remove repressive complexes, open the chromatin via the modification of the core and linker histones and recruit transcriptional activators and transcription machinery. A straightforward principle perhaps, but complicated by the multiplicity of enzyme activities, post-translational modifications and crosstalk mechanisms. Adding to this, these processes themselves are regulated by extracellular signals, resulting in the activation of signaling cascades that transmit the signal to the nucleus and ultimately to chromatin. The importance of chromatin-modifying enzymes and transcription factors in cancer is well-established; however, the complexity of signaling to chromatin makes challenging the identification of effective potential targets for the treatment of cancer.