The role for runt related transcription factor 2 (RUNX2) as a transcriptional repressor in luteinizing granulosa cells

Eun Sil Park; Jiyeon Park; Renny T. Franceschi; Misung Jo

doi:10.1016/j.mce.2012.06.005

The role for runt related transcription factor 2 (RUNX2) as a transcriptional repressor in luteinizing granulosa cells

Eun Sil Park, Jiyeon Park, Renny T. Franceschi, Misung Jo

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

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 48h. The knockdown of the agonist-stimulated Runx2 expression increased Runx1, Ptgs2, and Tnfaip6 expression and PGE₂ levels in luteinizing granulosa cells. Conversely, the over-expression of RUNX2 inhibited the expression of these genes and PGE₂ 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.

Original language	English
Pages (from-to)	165-175
Number of pages	11
Journal	Molecular and Cellular Endocrinology
Volume	362
Issue number	1-2
DOIs	https://doi.org/10.1016/j.mce.2012.06.005
State	Published - Oct 15 2012

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grants by R01HD061617 and R03HD066012 (to M.J.).

Keywords

Granulosa cells
LH
Ptgs2
Runx1
Runx2
Tnfaip6

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Endocrinology

Access to Document

10.1016/j.mce.2012.06.005

Cite this

@article{7abf095d9a96434da046c14b6ac5680d,

title = "The role for runt related transcription factor 2 (RUNX2) as a transcriptional repressor in luteinizing granulosa cells",

abstract = "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 48h. The knockdown of the agonist-stimulated Runx2 expression increased Runx1, Ptgs2, and Tnfaip6 expression and PGE2 levels in luteinizing granulosa cells. Conversely, the over-expression of RUNX2 inhibited the expression of these genes and PGE2 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.",

keywords = "Granulosa cells, LH, Ptgs2, Runx1, Runx2, Tnfaip6",

author = "Park, {Eun Sil} and Jiyeon Park and Franceschi, {Renny T.} and Misung Jo",

note = "Funding Information: This work was supported by National Institutes of Health Grants by R01HD061617 and R03HD066012 (to M.J.). ",

year = "2012",

month = oct,

day = "15",

doi = "10.1016/j.mce.2012.06.005",

language = "English",

volume = "362",

pages = "165--175",

number = "1-2",

}

TY - JOUR

T1 - The role for runt related transcription factor 2 (RUNX2) as a transcriptional repressor in luteinizing granulosa cells

AU - Park, Eun Sil

AU - Park, Jiyeon

AU - Franceschi, Renny T.

AU - Jo, Misung

N1 - Funding Information: This work was supported by National Institutes of Health Grants by R01HD061617 and R03HD066012 (to M.J.).

PY - 2012/10/15

Y1 - 2012/10/15

N2 - 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 48h. The knockdown of the agonist-stimulated Runx2 expression increased Runx1, Ptgs2, and Tnfaip6 expression and PGE2 levels in luteinizing granulosa cells. Conversely, the over-expression of RUNX2 inhibited the expression of these genes and PGE2 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.

AB - 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 48h. The knockdown of the agonist-stimulated Runx2 expression increased Runx1, Ptgs2, and Tnfaip6 expression and PGE2 levels in luteinizing granulosa cells. Conversely, the over-expression of RUNX2 inhibited the expression of these genes and PGE2 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.

KW - Granulosa cells

KW - LH

KW - Ptgs2

KW - Runx1

KW - Runx2

KW - Tnfaip6

UR - http://www.scopus.com/inward/record.url?scp=84865292066&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865292066&partnerID=8YFLogxK

U2 - 10.1016/j.mce.2012.06.005

DO - 10.1016/j.mce.2012.06.005

M3 - Article

C2 - 22713854

AN - SCOPUS:84865292066

SN - 0303-7207

VL - 362

SP - 165

EP - 175

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

IS - 1-2

ER -

The role for runt related transcription factor 2 (RUNX2) as a transcriptional repressor in luteinizing granulosa cells

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this