Histone acetyl transferases (HATs) promote opening of the chromatin and enhance transcription, whereas histone de-acetylases (HDACs) have the opposite effect (49–51). The ability of CIITA to recruit HATs, including KAT2A (also known as pCAF-B) and NCOA1 (also known as SRC-1), to the promoter of the major histocompatibility complex-II (MHC-II) gene, has been extensively studied in macrophages (52, 53). Given the previous literature, CIITA upregulation by IFN-γ could be seen as a positive control for our array study. However, we also found CIITA to be upregulated to a lesser extent by IL-4, and both effects were independent of cell proliferation. Upregulation of NCOA1 selectively by IFN-γ most likely enhances the effects CIITA (52, 53) but downregulation of KAT2A seems paradoxical. However, this might also enhance the action of IFN-γ by decreasing acetylation and potentiating the functions of IRFs (54). The HAT, ESCO2, was also downregulated by IFN-γ or IL-4, although from our data this appeared to be mainly the consequence of the inhibition of cell proliferation. As its full name “Establishment of Sister Chromatid Cohesion N-Acetyltransferase” implies, ESCO2 has a known role in mitosis (30). It functions as part of the cohesion complex and its mutation leads to the cohesinopathy, Roberts syndrome (55). However, cohesin (and perhaps therefore ESCO2) has also been ascribed a wider role in gene transcription (56–58) and ESCO2 participates in Notch signaling (59), observations that might have implications for proliferating macrophages, although this remains to be investigated. Overall, our results imply that treatment with IFN-γ has the ability to both increase and decrease activity of specific HATs, thereby increasing or decreasing expression of different genes. In future experiments, beyond the present scope, it will be interesting to investigate the effects of manipulating levels of the HATs we have identified as up- or downregulated on both positive and negative transcriptional responses to IFN-γ. Recent data from the group of de Winther and colleagues showed, for example, that IFN-γ treatment specifically altered the acetylation status of the promoters of two downregulated genes, Il1b and Il6, in mouse macrophages (60), although the role of specific HATs and HDACs in these changes was not defined. We did not detect effects of IFN-γ or IL-4 on mRNA expression of any of the HDACs-1 to -11 that were included in our RT-qPCR screen. However, other mechanisms including changes in recruitment and activation of HATs and HDACs at specific promoters also contributes to acetylation status (61).