Background: Research on chromatin regulators (CRs) becomes hotspot as the discovery that CRs havc functions on regulating posttranslational modifications of histones, including acetylation, methylation, ubiquitinylation and so on.CRs can add ("writer"), remove ("eraser"), or bind ("reader") histone modifications, playing an important role in gene regulation.It is a compelling hypothesis that different combinations of chromatin regulators (CRs) might contribute to different histone modification states.PHF8 is a JmjC domain-containing protein and is recruited by its PHD domain based on interaction with H3K4me3, which can demethylate H4K20mel and H3K9mel/2.H3K4me3 enriched at RNA polymerase Ⅱ (RNAPII) transcription start sites (TSSs), usually considered to be an activating chromatin mark.On the other hand, H4K20mel and H3K9mel/2 are repressive histone marks.Above all, indicating that PHF8 is an activator in gene regulation.PHF8 has been rcported interacting with ZNF711, both of which are X-linked mental retardation (XLMR) protein, and their results also indicate that PHF8, ZNF711 and JARID1C/ SMCX are linked in a pathway suppressing XLMR.It has also been reported that PHF8 can interact with E2F1, regulating the cell cycle biological process by removing the H4K20mel mark from a subset of E2F 1-regulated gene promoters.Results: We discussed the relationship of two chromatin regulators PHF8 and NRSF.No research before has related to this, though a lot of studies and experiments carried out on them separately.Here we try to see these two together, by bioinformatics methods.Interestingly, when we do the motif finding analysis for PHF8 ChIP-seq results, the canonical motif of REST/NRSF is on the top of the list, but not found in neuronal cell line.ChIP-seq data were from public database GSE20725, GSE22478 and GSE20763, all were provided by elite groups on PHF8.Conclusions: PHF8 is associated with NRSF to up gene expression, but it down regulated gene expression with E2F1 in Hela cell line .