Effect of estradiol on histone acetylation dynamics in human breast cancer cells

Histone acetylation plays an important role in remodeling chromatin structure, facilitating nuclear processes such as transcription. We investigated the effect of estradiol on global histone acetylation in hormone-responsive human breast cancer cells. Pulse-chase experiments and immunoblot analyses of dynamically acetylated histones show that estradiol rapidly increases histone acetylation in estrogen receptor (ER)positive, hormone-dependent T5, but not in ER-negative, hormone-independent MDA MB 231 breast cancer cells. The effect of estradiol on the rates of histone acetylation and deacetylation in T5 cells was determined. We found that estradiol increased the level of acetylated histories by reducing the rate of histone deacetylation, whereas the rate of histone acetylation was not altered. Enzymatic assays and immunoblot analyses of cell fractions showed that estradiol did not affect the level, sub-nuclear distribution, or activity of class I and II histone deacetylases. However, estradiol did alter the intranuclear distribution of ER and histone acetyltransferases, with both becoming tightly bound in the nucleus and associated with the nuclear matrix. We propose that, following the association of ER with nuclear matrix sites, ER alters the balance of historic acetyltransferases and histone deacetylases at these sites and the dynamics of acetylation of histories associated with transcriptionally active and competent chromatin.