ELK1 is a member of the ternary complex factor subfamily of ETS transcription factors and intriguingly, our unbiased computational analysis of the NAc microarray data also identified ETS1, the prototype of the ETS1 family, as enriched in the promoter region of down-regulated genes of heroin abusers. In addition to cellular remodeling linked to synaptic plasticity, ETS1 family members are known to play important roles in various cellular functions such as proliferation,(68) differentiation,(69) migration,(70) and apoptosis.(71) Other transcriptional regulators implicated in addiction such as CREB also target some genes common to ELK1. By focusing on gene targets regulated by ELK1 in a CREB- and SRF-independent manner, we confirmed reduction of the genes BAG1 and USE1 identified in the microarray. BAG1 has antiapoptotic effects that confer prosurvival signals to enhance neurite outgrowth activity and is activated downstream of RAF1 and MEK activity.(72–74) 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,
