The role for runt related transcription factor 2 (RUNX2) as a transcriptional repressor in luteinizing granulosa cells.
Transcription factors induced by the LH surge play a vital role in reprogramming the gene expression in periovulatory follicles. The present study investigated the role of RUNX2 transcription factor in regulating the expression of Runx1, Ptgs2, and Tnfaip6 using cultured granulosa cells isolated from PMSG-primed immature rats. hCG or forskolin+PMA induced the transient increase in Runx1, Ptgs2, and Tnfaip6 expression, while the expression of Runx2 continued to increase until 48 h. The knockdown of the agonist-stimulated Runx2 expression increased Runx1, Ptgs2, and Tnfaip6 expression and PGE(2) levels in luteinizing granulosa cells. Conversely, the over-expression of RUNX2 inhibited the expression of these genes and PGE(2) levels. The mutation of RUNX binding motifs in the Runx1 promoter enhanced transcriptional activity of the Runx1 promoter. The knockdown and overexpression of Runx2 increased and decreased Runx1 promoter activity, respectively. ChIP assays revealed the binding of RUNX2 in the Runx1 and Ptgs2 promoters. Together, these novel findings provide support for the role of RUNX2 in down-regulation of Runx1, Ptgs2, and Tnfaip6 during the late ovulatory period to support proper ovulation and/or luteinization.
Department of Obstetrics and Gynecology, Chandler Medical Center, University of Kentucky, Lexington, KY 40536-0298, USA.
Eun-Sil
ES
Park
Jiyeon
J
Park
Renny T
RT
Franceschi
Misung
M
Jo
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology / Q000502:physiology; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006107:Granulosa Cells / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D034461:Luteinization; D010053:Ovary / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic; D000099186:Histone Deacetylase 3
D015815:Cell Adhesion Molecules; D006063:Chorionic Gonadotropin; D050659:Core Binding Factor Alpha 1 Subunit; D050676:Core Binding Factor Alpha 2 Subunit; D051546:Cyclooxygenase 2; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D049410:Luciferases, Renilla; D012097:Repressor Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D000099186:Histone Deacetylase 3; C493727:Runx1 protein, rat; C493717:Runx2 protein, rat; C099683:SIN3A transcription factor; C513056:Tnfaip6 protein, rat; C489691:Ptgs2 protein, rat; C515890:Hdac1 protein, rat