Abstract
Despite their essential role in vertebrate development, the function of Pax proteins in gene regulation is not well understood. To identify potential genes regulated by the Pax2 protein, we screened embryonic kidney cells transformed with Pax2-expressing retroviruses for genes activated in response to Pax2 expression. In this system, the gene encoding the secreted frizzled related protein, Sfrp2, was strongly activated in all Pax2b-expressing cells. This activation of Sfrp2 expression correlated with changes in chromatin structure at the Sfrp2 locus, particularly in and around regions of Pax2 binding. Although the amount of Pax2-dependent transactivation was low in transient assays, the data suggests that local alterations of chromatin structure by Pax proteins can greatly enhance expression when presented in the right cellular context.
Highlights
§ A recipient of the American Society of Nephrology Gottschalk Award and supported in part by a fellowship from the Polycystic Kidney Research Foundation
To identify potential genes regulated by the Pax2 protein, we screened embryonic kidney cells transformed with Pax2-expressing retroviruses for genes activated in response to Pax2 expression
To identify potential target genes activated by the Pax2 transcription factor, we developed a panel of immortalized cell lines derived from metanephric mesenchyme of E11 ImmortoMouseTM embryos
Summary
§ A recipient of the American Society of Nephrology Gottschalk Award and supported in part by a fellowship from the Polycystic Kidney Research Foundation. Modification of Pax activity by JNK is attenuated by the Groucho 4 protein, which is able to completely suppress Pax transactivation ability [27] These lines of investigation suggest multiple functions of Pax that may be determined in part by different sets of positively and negatively regulated target genes. Both in the developing kidney and nervous system, Pax protein activity plays an essential role in cellular differentiation, cell survival, and tissue remodeling. To try and identify potential genes downstream of the Pax protein, we developed cell lines from immortalized mouse kidney mesenchyme that were Pax2-negative and introduced the Pax protein. These data suggest that Sfrp is a target of the Pax transcription factor, late in epithelial cell polarization
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
