title: Effect of estradiol on histone acetylation dynamics in human breast cancer cells.
abstract: 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 histones 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, subnuclear 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 histone acetyltransferases and histone deacetylases at these sites and the dynamics of acetylation of histones associated with transcriptionally active and competent chromatin.
authors.affiliation: Manitoba Institute of Cell Biology, Winnipeg, Manitoba R3E 0V9, Canada.
authors.forename: J M
authors.initials: JM
authors.lastname: Sun
authors.forename: H Y
authors.initials: HY
authors.lastname: Chen
authors.forename: J R
authors.initials: JR
authors.lastname: Davie
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D002458:Cell Fractionation; D003513:Cycloheximide / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D051548:Histone Acetyltransferases; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D020033:Protein Isoforms; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014407:Tumor Cells, Cultured
chemical_list: D006657:Histones; D020033:Protein Isoforms; D011500:Protein Synthesis Inhibitors; D011960:Receptors, Estrogen; D029701:Saccharomyces cerevisiae Proteins; D004958:Estradiol; D003513:Cycloheximide; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases