Unfortunately, Bag1 shares an ELK1 promoter binding site with another gene in close proximity, Chmp5, which makes the assessment of transcription factor binding difficult to distinguish with ChIP.(56) We were, nevertheless, able to detect ELK1 at the promoter of Use1, a gene known to be antiapoptotic (75), and to act as an E2 ubiquitin-conjugating enzyme to aide in the proteasomal degradation of proteins.(76) ELK1 occupancy at Use1 was decreased 1 hour after heroin self-administration, validating direct gene transcription regulation in the NAc after repeated heroin exposure. ELK1 occupancy at the Use1 promoter was normalized 24 hours later, in line with the dynamic nature of transcription factors. Clearly, the time course of ELK1 regulation is an important question. Moreover, while the current study focused on SRF-independent downstream targets, SRF-dependent ELK1 transcriptional activity is also relevant to addiction and warrants future studies in heroin abuse.
