Molecular Cell
Volume 7, Issue 1, 1 January 2001, Pages 137-149
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Article
Two-Step Regulation of Left–Right Asymmetric Expression of Pitx2: Initiation by Nodal Signaling and Maintenance by Nkx2

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Abstract

Pitx2 is left–right (L–R) asymmetrically expressed initially in the lateral plate and later in primordial visceral organs. The transcriptional regulatory mechanisms that underlie L–R asymmetric expression of Pitx2 were investigated. Mouse Pitx2 has a left side–specific enhancer (ASE) that mediates both the initiation and maintenance of L–R asymmetric expression. This element contains three binding sites for the transcription factor FAST. The FAST binding sites function as Nodal-responsive elements and are sufficient for the initiation but not for the maintenance of asymmetric expression. The maintenance requires an Nkx2-5 binding site also present within the ASE. These results suggest that the left-sided expression of Pitx2 is directly initiated by Nodal signaling and is subsequently maintained by Nkx2. Such two-step control may represent a general mechanism for gene regulation during development.

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