Extended Data Figure 2. ChIP-seq analysis of REST target genes shows enrichment for genes related to cell death and the pathology of AD.

a. Genes identified by REST ChIP-seq in SH-SY5Y cells are downregulated in the aging human PFC. Expression of age-regulated REST target genes identified by ChIP-seq shows a highly significant inverse correlation with age at death. For each case, a weighted expression index was derived for age-regulated target genes based on microarray analysis. These values were normalized to the youngest adult value (24 yrs; 100%). N=43, age range 24–106 yrs. b. Canonical pathways by Ingenuity IPA analysis of REST ChiP-seq targets. c. REST ChIP-seq binding peaks in genes related to cell death pathways and AD pathology. d. Confirmation of ChIP-seq targets by quantitative ChIP-PCR following REST overexpression (OE-REST) or REST knockdown (sh-RESTa and sh-RESTb) in SH-SY5Y cells. Shown is ChIP followed by real time PCR using primers that amplify REST binding sites identified by ChIP-seq. PCR amplification of a region of the actin promoter not proximal to a known RE1 site was used as a negative control. Values are normalized to the input control and represent the mean±S.E.M., n=3. ^*P<0.05 relative to control by Student’s unpaired t-test.