Estrogen mediates phosphorylation of histone H3 in ovarian follicle and mammary epithelial tumor cells via the mitotic kinase, Aurora B.
Cells of the ovarian follicle undergo extensive proliferation and differentiation from the time that the follicle escapes from the primordial state to its acquisition of ovulatory capacity. We examined the dynamic modification of the phosphorylation state of the histone H3 N-terminal tail in granulosa cells during follicular development. In rodent follicles, the granulosa cell H3 phosphorylation on Ser10 peaks during proestrus. This epigenetic mark is induced by both FSH and 17beta-estradiol (E2), acting independently. E2-induced H3 phosphorylation fails to occur in mice with inactivated alpha-isoform of the nuclear estrogen receptor. E2 induction of histone phosphorylation is attenuated by cell cycle inhibition. Further, E2 induces the activity of the mitotic kinase, Aurora B, in a mammary tumor cell model where mitosis is estrogen receptor-alpha dependent. These results provide evidence for mitotic regulation in follicle development by estrogen and demonstrate a previously undiscovered mechanism for induction of cell proliferation in ovarian and mammary gland cells.
Ruiz-Cortés
Z Tatiana
ZT
Centre de recherche en reproduction animale, Faculté de médecine vétérinaire, Université de Montréal, St-Hyacinthe, Quebec, Canada J2S 7C6.
Kimmins
Sarah
S
Monaco
Lucia
L
Burns
Kathleen H
KH
Sassone-Corsi
Paolo
P
Murphy
Bruce D
BD
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001943:Breast Neoplasms / Q000201:enzymology*; D002453:Cell Cycle / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D047629:Estrogen Receptor beta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis / Q000187:drug effects; D006080:Ovarian Follicle / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D011359:Proestrus / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006657:Histones; D004958:Estradiol; D005640:Follicle Stimulating Hormone; C576921:AURKB protein, human; C576924:Aurkb protein, mouse; C576925:Aurkb protein, rat; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases