Kobayashi Masatomo, Fujioka Miki, Tolkunova Elena N, Deka Deepali, Abu-Shaar Muna, Mann Richard S, Jaynes James B
Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Development. 2003 Feb;130(4):741-51. doi: 10.1242/dev.00289.
Engrailed is a key transcriptional regulator in the nervous system and in the maintenance of developmental boundaries in Drosophila, and its vertebrate homologs regulate brain and limb development. Here, we show that the functions of both of the Hox cofactors Extradenticle and Homothorax play essential roles in repression by Engrailed. Mutations that remove either of them abrogate the ability of Engrailed to repress its target genes in embryos, both cofactors interact directly with Engrailed, and both stimulate repression by Engrailed in cultured cells. We suggest a model in which Engrailed, Extradenticle and Homothorax function as a complex to repress Engrailed target genes. These studies expand the functional requirements for extradenticle and homothorax beyond the Hox proteins to a larger family of non-Hox homeodomain proteins.
Engrailed是果蝇神经系统中关键的转录调节因子，在维持发育边界方面发挥作用，其脊椎动物同源物则调节大脑和肢体发育。在此，我们表明Hox辅因子Extradenticle和Homothorax的功能在Engrailed的抑制作用中都起着至关重要的作用。去除其中任何一个的突变都会消除Engrailed在胚胎中抑制其靶基因的能力，这两个辅因子都直接与Engrailed相互作用，并且都能在培养细胞中刺激Engrailed的抑制作用。我们提出了一个模型，其中Engrailed、Extradenticle和Homothorax作为一个复合物发挥作用，以抑制Engrailed的靶基因。这些研究将Extradenticle和Homothorax的功能需求从Hox蛋白扩展到了更大的非Hox同源域蛋白家族。
