title: Histone deacetylase 1 (HDAC1) regulates retinal development through a PAX6-dependent pathway.
abstract: Cell fate determination is tightly controlled by the expression of transcription factors and gene regulatory networks. PAX6 is a transcription factor containing a DNA-binding paired-box domain and homeobox domain that plays a key role in the development of the eye, brain, and pancreas. Here, we showed that histone deacetyltransferase 1 (HDAC1) is a novel binding partner of PAX6 in newborn mouse retinas. We also showed that HDAC1 specifically binds to the paired and transactivation domains of PAX6, and these physical interactions were required for effective repression of PAX6 transcriptional activity during retinal development. Furthermore, HDAC1 preferentially regulates the transcriptional activity of PAX6 when it binds to paired-domain (P6CON and chimeric pCON/P3) PAX6 responsive elements compared to homeodomain (pP3) PAX6 responsive elements. The repressive effect of HDAC1 on the transcriptional activity of PAX6 was reversed by knockdown of HDAC1 or treatment with an HDAC inhibitor, TSA. Taken together, these results show that HDAC1 binds PAX6 and that protein-protein interaction leads to transcriptional repression of PAX6 target genes during mouse retinal development.
authors.affiliation: Genome Dynamics Laboratory, Department of Life Science, Chung-Ang University, Seoul 06974, Republic of Korea.
authors.forename: Chul-Hong
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Genome Dynamics Laboratory, Department of Life Science, Chung-Ang University, Seoul 06974, Republic of Korea.
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: An
authors.affiliation: Genome Dynamics Laboratory, Department of Life Science, Chung-Ang University, Seoul 06974, Republic of Korea.
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Genome Dynamics Laboratory, Department of Life Science, Chung-Ang University, Seoul 06974, Republic of Korea. Electronic address: jungkim@cau.ac.kr.
authors.forename: Jung-Woong
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018274:Electroporation; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D000071841:PAX6 Transcription Factor / Q000378:metabolism*; D000072417:Protein Domains; D025941:Protein Interaction Mapping; D012160:Retina / Q000254:growth & development*
chemical_list: D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; C000605732:Pax6 protein, mouse; C110550:HDAC1 protein, human; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1
keywords: Development; HDAC1; PAX6; Protein-protein interaction; Retina; Transcriptional regulation