cRNA microarray and real-time PCR (qPCR) studies identified a number of Estrogen Signaling Pathway (ESP) genes (GTF2H2, NCOR1, TAF9, NRAS, NRIP1, POLR2A, DDX5, NCOA3) and Cell Cycle Pathway genes (CCNA2, PCNA, CDKN1A, CCND1, PLK1) in MCF-7 breast cancer cells that are regulated by the bioflavonoid luteolin. Chromatin immunoprecipitation (ChIP) studies revealed that luteolin modified histone H4 acetylation at the PLK-1 promoter suggesting that this bioflavonoid controls gene transcription via an epigenetic mechanism involving histone H4 acetylation. These findings are consistent with the anti-estrogenic and anti-proliferative properties of luteolin in normal and malignant cells.