Two-Step Regulation of Left–Right Asymmetric Expression of Pitx2

Autor: Hiroshi Hamada, Kyoko Mochida, Hiromi Hashiguchi, Rui Sakuma, Jinsuke Nishino, Yukio Saijoh, Hidetaka Shiratori, Minoru Watanabe, Yasuo Sakai, Malcolm Whitman
Rok vydání: 2001
Předmět:
Zdroj: Molecular Cell. 7(1):137-149
ISSN: 1097-2765
DOI: 10.1016/s1097-2765(01)00162-9
Popis: 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.
Databáze: OpenAIRE