Histone methyl transferases (HMTs) and lysine de-methylases (KDMs) can be stimulatory or inhibitory to transcription depending on the site and degree of methylation that is optimal (62). For example, H3K4 methylation has important consequences for both enhancer and promoter activity of macrophage specific genes (63). Mono and di-methylation appear permissive for enhancers but tri-methylation for promoters of LPS-sensitive genes (61). A previous study on human macrophages stimulated with LPS and IFN-γ (64) showed increased H3K4 methylation associated with increased expression of the HMT, myeloid lymphoid leukemia (MLL). Given that we did not see any change in MLL expression with IFN-γ alone (absent from Table 2), it is possible that this is an effect of LPS, although this requires verification. In our study, the HMTs, PRMT7, SETD6, and SMYD3, were downregulated after priming by IFN-γ alone, independently of inhibition of proliferation. PRMT7 is a member of the PRMT histone arginine methylases, whereas SETD6 and SMYD3 are lysine methyl transferases. PRMT7 upregulates expression of metalloproteinase-9 (MMP-9) (65) in breast carcinoma cells but its role in macrophages is unknown. The related PRMT4 promotes major histocompatibility II (MHCII) gene expression (52). SETD6 activity has been linked to repression of the nuclear factor κB (NF-κB) system (66, 67) and upregulation of estrogen-responsive genes (68) in other cell types but there appears to have been very little previous work in mouse or human macrophages beyond demonstrating its presence preferentially in alternatively activated human macrophages, consistent with our results (64). SMYD3 di- and tri-methylates H3K4 residues (62). Although not an S-phase gene, SMYD3 has been identified as essential for cancer cell proliferation (69). It also plays a role in rescue from senescence (70), estrogen response (71), and MMP-9 induction (72) in various cancer cell lines. SMYD3 is also little studied in macrophages, although a previous study demonstrated its downregulation by a combination of LPS and IFN-γ, which is consistent with our findings (64).