April 2010

[JBC] Coordinating T-box Expression

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Tbx1, Tbx2, Tbx5 and Tbx6 show upregulated spatial expression in Pitx2-deficient mutant embryos (highlighted by arrows and an asterisk).

The transcription factor Pitx2 is critical for the development of multiple tissues and organs by promoting proper body-wall formation and closure, although how Pitx2 influences these events is unclear. A likely mechanism might involve the regulation of the T-box family of developmental transcription factors. In this study, the researchers examined abdominal tissue in 10.5-day-old mouse embryos and identified seven T-box genes as targets of Pitx2 at various locations; Tbx4, Tbx15 and Mga were activated by Pitx2 while Tbx1, Tbx2, Tbx5 and Tbx6 were repressed. Chromatin analysis revealed that Pitx2 bound to multiple sites around these genes, both upstream and within introns, along with selected co-repressors or co-activators. Pixt2-dependent occupancy of co-repressors generally resulted in reduced acetylation levels of several T-box genes, whereas Pitx2-dependent occupancy of co-activators showed less consistent chromatin patterns, suggesting they operate in a more site-localized or indirect mechanism. Although Pitx2 is part of a complex gene network, and likely regulates organ development through other signaling pathways, these studies provide the groundwork to better understand abdominal wall defects.

Pitx2-dependent Occupancy by Histone Deacetylases Is Associated with T-box Gene Regulation in Mammalian Abdominal Tissue

Traci Hilton, Michael K. Gross and Chrissa Kioussi

J. Biol. Chem., published online Feb. 3, 2010 

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