KLF11 epigenetically regulates glycodelin-A, a marker of endometrial biology via histone-modifying chromatin mechanisms.
Endometrial biology is characterized by programmed proliferation and differentiation that is synchronous with ovarian folliculogenesis to maximize the chance of pregnancy. Glycodelin-A, an endometrial secretory protein, promotes pregnancy mostly through immunomodulatory mechanisms. Glycodelin-A is repressed during the proliferative and early secretory phase and activated thereafter. Progesterone activates glycodelin via the Sp1 (Specificity Protein 1) transactivator. We identify a novel role for Kruppel-like transcription factor 11 (KLF11) as a glycodelin-A repressor. Although KLF11 bound 2 distinct regulatory elements, it regulated glycodelin promoter activity differentially through each element. Whereas KLF11 weakly activated glycodelin promoter activity via a region that also bound Sp1, the dominant effect of KLF11 was repression of promoter activity, messenger RNA (mRNA), and protein expression via a novel, specific binding element. KLF11 mediated this repression by recruiting the SIN3/histone deacetylase (HDAC) corepressor complex to the glycodelin promoter. KLF11 may solely, or by competing with Sp1, repress glycodelin-A levels and thereby influence its role in the endometrium.
1Laboratory of Translational Epigenetics in Reproduction, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA.
Zaid M
ZM
Tabbaa
Ye
Y
Zheng
Gaurang S
GS
Daftary
D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D002843:Chromatin / Q000502:physiology*; D004717:Endometrium / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000502:physiology*; D006657:Histones / Q000502:physiology*; D006801:Humans; D012097:Repressor Proteins / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D000071816:Glycodelin; D006023:Glycoproteins; D006657:Histones; C115117:KLF11 protein, human; C045246:PAEP protein, human; D012097:Repressor Proteins
KLF11; SIN3/HDAC; endometrium; glycodelin-A; repressor