A similar overlap was observed in ER binding sites detected in MCF-7 cells by ChIP-seq and ChIP-chip . Lastly, the analysis methods used to generate the published data were likely different than used in our study. This information is not currently available for the published data. Nuclear receptors, including PR, have been shown to associate with DNA independently of Paclitaxel hormone response elements, by tethering to AP-1 . In the case of ER, this mechanism was reported to mediate transcriptional repression of target transcripts by estrogen . These findings suggest that AP-1 binding sites may be more common in binding regions that lack PREs and could be associated with down-regulated genes. AP-1 sites were present in 27% of regions that contained PREs and 29% of regions lacking PREs in AB32 binding regions. This proportion was higher overall than in T-47D cells where AP-1 site enrichment was not observed , however it was not different between the two subsets of binding regions. There was also no evidence that AP1 sites were more prevalent in downregulated than up-regulated genes . These data suggest that, while AP-1 may co-operate with PR on a subset of binding sites in AB32 cells, its role in progesterone signaling may be more minor than for estrogen. Binding of the transcriptional cofactor NF1 to DNA requires coassociation by PR, and NF1 and PR have synergistic effects on gene expression , demonstrating the potential for coexpression of these transcription factors to result in enhanced transcriptional outcomes. In the mammary gland, the coordinated expression of NF1 isoforms is involved in controlling lactation and involution . NF1 action in the mammary gland is contextspecific, and is induced when mammary epithelial cells are maintained in contact with laminin-rich RWJ 64809 purchase extracellular matrix . The development-specific and context-specific actions of NF1 in the mammary gland suggest that its interplay with PR may be regulated by both NF1 and PR levels, and that these may be susceptible to modulation under physiological circumstances that include carcinogenesis. Enrichment of NF1 binding motifs in PR binding regions in AB32 cells, but not breast cancer cells, supports this view and suggests that NF1 is a cell type-restricted PR cofactor. Our data suggest that a combination of chromatin remodelling cofactors is important for progesterone response in the breast and that the relative expression and coordinated action of these cofactors determines the PR cistrome. Progesterone has a diverse range of effects in normal and malignant target tissues and the results of this study demonstrate that the interplay between key cofactors and PR on the progesterone regulated cistrome contributes to context specificity of progesterone action, and may play a central role in aberrant progestin effects in breast cancer.