the CoREST complex to target gene promoters. ChIP experiments were performed using shNurr1- or shCtrl-BV2 cells. In the absence of Nurr1, CoREST was not recruited to the TNFα-promoter (Fig. 4H, left panel). Interestingly, under these conditions, p65 was present at the TNFα-promoter for extended times (Fig. 4H, right panel). Regulation of p65 acetylation by HDACs, including HDAC1, is known to determine the duration of transcription (Ashburner et al., 2001). HDAC1 is recruited to TNFα or iNOS-promoter in an LPS-dependent manner; however, this recruitment is severely impaired in the absence of Nurr1 (Fig. S9E). Finally, to verify an in vivo role for the genes identified to be involved in Nurr1/CoREST transrepression pathway, BV2 cells were transfected with siRNAs targeting their corresponding mRNAs and were tested for the ability to increase the production of neurotoxic factors. As shown in Figure S10A, knockdown of each of the molecules engaged in this Nurr1/CoREST-mediated transrepression pathway induced significantly higher death of Neuro2A cells compared to control siRNA, as detected by TUNEL ELISA assay
