Pax6 is a member of the Pax family of transcription factors that contains a DNA binding paired-box and homeobox domain. In animals, including humans, Pax6 plays a key role in development, regulating organogenesis of the eye and brain. The current data show that histone acetyltransferase Tip60 physically interacts with Pax6 in developing post-natal day 4 (P4) mouse retinas. We also found that Tip60 binds with paired-domain of Pax6 using its chromo- and zinc-finger-containing regions, and that these protein interactions were needed for the effective full-transcriptional activation of Pax6. Furthermore, among the combinations of Pax6-target gene interactions using its two DNA binding domain, paired- and homeobox domain, Tip60 significantly enhanced the transcriptional activity of Pax6 on the paired-domain binding sequence (P6CON) containing reporter construct (pCON) than other homeo domain and chimera binding containing pP3 and pCON/P3 constructs. Taken together, these results suggest that Tip60 binds with Pax6 and that this physical interaction leads to the full-transcriptional activation of Pax6 during retina development. (C) 2012 Elsevier Inc. All rights reserved.