Detrimental role of GATA transcription factors on Gnrhr expression is counterbalanced by LIM homeodomain proteins through a bi-functional response element

2012 ◽  
Vol 73 (2) ◽  
pp. 149
Author(s):  
Anne-Laure Schang ◽  
Anne Granger ◽  
Bruno Quérat ◽  
Joëlle Cohen-Tannoudji ◽  
Jean-Noël Laverrière
2011 ◽  
Vol 286 (50) ◽  
pp. 42971-42980 ◽  
Author(s):  
Morgan S. Gadd ◽  
Mugdha Bhati ◽  
Cy M. Jeffries ◽  
David B. Langley ◽  
Jill Trewhella ◽  
...  

2013 ◽  
Vol 27 (1) ◽  
pp. 74-91 ◽  
Author(s):  
Anne-Laure Schang ◽  
Anne Granger ◽  
Bruno Quérat ◽  
Christian Bleux ◽  
Joëlle Cohen-Tannoudji ◽  
...  

GATA2 transcription factor and LIM homeodomain proteins Islet1 (ISL1) and LIM homeobox 3 (LHX3) are suspected to be involved in gonadotrope cell fate and maintenance. The GnRH receptor gene (Gnrhr), crucial for gonadotrope function, is expressed in the pituitary gland from embryonic day 13.5 onward, well before LH and FSH β-subunits. This expression pattern together with the presence of WGATAR and TAAT motifs in Gnrhr promoter sequences suggests the involvement of early transcription factors in promoter activation. In this study, using a well-characterized transgenic mouse model, GATA2 was found colocalized with Gnrhr promoter activity in the pituitary. Transient transfection of Gnrhr promoter luciferase fusion constructs together with either GATA2 expression vectors or small interfering RNA in gonadotrope cell lines indicated that GATA2, which typically acts as a trans-activator, unexpectedly repressed Gnrhr promoter activity. Using DNA chromatography affinity and EMSA, we demonstrated that GATA2 operates via a response element containing a peculiar palindromic GATA motif that overlaps a critical TAAT motif involved in LHX3/ISL1 trans-activation. Indeed, despite the inhibitory action of GATA2, this element displayed a clear-cut enhancer activity in gonadotrope cells. Chromatin immunoprecipitation assays indicated that GATA2, LHX3, and ISL1 interact with a Gnrhr promoter fragment encompassing this element. The trans-repressive action of GATA2 on Gnrhr promoter activity is likely balanced or even hindered by trans-activating effects of LIM homeodomain proteins via this novel bifunctional LIM/GATA response element. Such a hierarchical interplay may contribute to finely adjust Gnrhr gene expression in gonadotrope cell lineage during pituitary development as well as in the adult animal.


Author(s):  
Marjolein HFM Lentjes ◽  
Hanneke EC Niessen ◽  
Yoshimitsu Akiyama ◽  
Adriaan P de Bruïne ◽  
Veerle Melotte ◽  
...  

The GATA family of transcription factors consists of six proteins (GATA1-6) which are involved in a variety of physiological and pathological processes. GATA1/2/3 are required for differentiation of mesoderm and ectoderm-derived tissues, including the haematopoietic and central nervous system. GATA4/5/6 are implicated in development and differentiation of endoderm- and mesoderm-derived tissues such as induction of differentiation of embryonic stem cells, cardiovascular embryogenesis and guidance of epithelial cell differentiation in the adult.


Oncotarget ◽  
2016 ◽  
Vol 7 (30) ◽  
pp. 47891-47903 ◽  
Author(s):  
Lijuan Xiao ◽  
Qin Feng ◽  
Zheng Zhang ◽  
Fen Wang ◽  
John P. Lydon ◽  
...  

Pneumologie ◽  
2012 ◽  
Vol 66 (06) ◽  
Author(s):  
HM Al-Tamari ◽  
M Eschenhagen ◽  
A Schmall ◽  
R Savai ◽  
HA Ghofrani ◽  
...  

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