Search for regulatory factors of the pituitary-specific transcription factor PROP1 gene

Abstract

Pituitary-specific transcription factor PROP1, a factor important for pituitary organogenesis, appears on rat embryonic day 11.5 (E11.5) in SOX2-expressing stem/progenitor cells and always coexists with SOX2 throughout life. PROP1-positive cells at one point occupy all cells in Rathke’s pouch, followed by a rapid decrease in their number. Their regulatory factors, except for RBP-J, have not yet been clarified. This study aimed to use the 3 kb upstream region and 1st intron of mouse prop1 to pinpoint a group of factors selected on the basis of expression in the early pituitary gland for expression of Prop1. Reporter assays for SOX2 and RBP-J showed that the stem/progenitor marker SOX2 has cell type-dependent inhibitory and activating functions through the proximal and distal upstream regions of Prop1, respectively, while RBP-J had small regulatory activity in some cell lines. Reporter assays for another 39 factors using the 3 kb upstream regions in CHO cells ultimately revealed that 8 factors, MSX2, PAX6, PIT1, PITX1, PITX2, RPF1, SOX8 and SOX11, but not RBP-J, regulate Prop1 expression. Furthermore, a synergy effect with SOX2 was observed for an additional 10 factors, FOXJ1, HES1, HEY1, HEY2, KLF6, MSX1, RUNX1, TEAD2, YBX2 and ZFP36Ll, which did not show substantial independent action. Thus, we demonstrated 19 candidates, including SOX2, to be regulatory factors of Prop1 expression.

Retinoic acid signalling is a candidate regulator of the expression of pituitary‐specific transcription factor Prop1 in the developing rodent pituitary

“…Our epigenetic analysis, however, suggested that Prop1 is not primarily regulated by DNA methylation except during the early period of Rathke's pouch formation . Subsequent transcription factor screening analysis by an in vitro reporter assay identified SOX2 as a predicted regulator for Prop1 ‐expression . Furthermore, although an in vivo study by Zhu et al .…”

“…Moreover, a reporter assay using truncated constructs of the mouse Prop1 upstream region identified two RA‐responsible regions (−1270/−444 appending DR5, DR0 and ER8, as well as −2993/−1841 appending DR3) as predicted cis ‐regulatory elements of RARα. We previously reported that SOX2, which consistently coexists in PROP1‐positive cells, markedly stimulates the promoter activity of these two regions: −1270/−444 and −2993/−1841 . Additionally, among these RAREs, DR0 (−1069/−1058) and ER8 (−1205/−1186) locate near a putative binding site for SOX2: TCAAG (−1137/−1132).…”

“…Construction of reporter vectors and expression vectors has been described previously . Briefly, serial truncated fragments of the 5′ ‐ upstream region of the mouse Prop1 gene (−2993/+21, −1840/+21, −1270/+21, −443/+21 and −154/+21) were obtained by PCR and ligated to the upstream site of the secreted alkaline phosphatase ( Seap ) gene in the pSEAP2‐Basic vector (BD Biosciences Clontech, Palo Alto, CA, USA) to construct the reporter vectors.…”

Long-chain unsaturated fatty acids reduce the transcriptional activity of the rat follicle-stimulating hormone β-subunit gene

“…3 ). In particular, FOXJ1, GLI1, MSX, PITX1, PRRX2, RUNX1, and SOX2 are expressed in the murine pituitary gland [ 37 , 38 , 39 , 40 , 41 , 42 ]. Therefore, unsaturated LCFAs may directly and/or indirectly modulate the binding of any of these factors.…”

GnRHa Treatment of Cryptorchid Boys Affects Genes Involved in Hormonal Control of the HPG Axis and Fertility

“…Furthermore, it was shown that SOX2 is able to modulate PROP1 expression and that various transcription factors might participate in the regulation of PROP1 in a SOX2 -dependent or independent manner. PROP1 is a pituitary-specific transcription factor that plays an important role in pituitary organogenesis and in the differentiation of hormone-producing cells [Nishimura et al, 2016]. In this context, it is intriguing that both SOX2 and PROP1 gene expression was elevated after GnRHa treatment (online suppl.…”