title: Histone Deacetylase 1 Is Essential for Rod Photoreceptor Differentiation by Regulating Acetylation at Histone H3 Lysine 9 and Histone H4 Lysine 12 in the Mouse Retina.
abstract: Histone acetylation has a regulatory role in gene expression and is necessary for proper tissue development. To investigate the specific roles of histone deacetylases (HDACs) in rod differentiation in neonatal mouse retinas, we used a pharmacological approach that showed that inhibition of class I but not class IIa HDACs caused the same phenotypic changes seen with broad spectrum HDAC inhibitors, most notably a block in the differentiation of rod photoreceptors. Inhibition of HDAC1 resulted in increase of acetylation of lysine 9 of histone 3 (H3K9) and lysine 12 of histone 4 (H4K12) but not lysine 27 of histone 3 (H3K27) and led to maintained expression of progenitor-specific genes such asVsx2andHes1with concomitant block of expression of rod-specific genes. ChiP experiments confirmed these changes in the promoters of a group of progenitor genes. Based on our results, we suggest that HDAC1-specific inhibition prevents progenitor cells of the retina from exiting the cell cycle and differentiating. HDAC1 may be an essential epigenetic regulator of the transition from progenitor cells to terminally differentiated photoreceptors.
authors.affiliation: From the Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, Pennsylvania 17033.|Laboratory of Evolutionary Genomics and Biocomplexity, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04039-032, Brazil.
authors.forename: Renata C
authors.initials: RC
authors.lastname: Ferreira
authors.affiliation: From the Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, Pennsylvania 17033.|Penn State Hershey Eye Center, Hershey, Pennsylvania 17033, and.
authors.forename: Evgenya Y
authors.initials: EY
authors.lastname: Popova
authors.affiliation: From the Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, Pennsylvania 17033.
authors.forename: Jessica
authors.initials: J
authors.lastname: James
authors.affiliation: Laboratory of Evolutionary Genomics and Biocomplexity, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04039-032, Brazil.
authors.forename: Marcelo R S
authors.initials: MR
authors.lastname: Briones
authors.affiliation: From the Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, Pennsylvania 17033.|Penn State Hershey Eye Center, Hershey, Pennsylvania 17033, and.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Zhang
authors.affiliation: From the Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, Pennsylvania 17033, cbarnstable@hmc.psu.edu.|Penn State Hershey Eye Center, Hershey, Pennsylvania 17033, and.
authors.forename: Colin J
authors.identifier: 0000-0002-7011-4068
authors.initials: CJ
authors.lastname: Barnstable
mesh_terms: D000107:Acetylation; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D012160:Retina / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000737:chemistry*; D012243:Rhodopsin / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D012243:Rhodopsin; D056284:Histone Deacetylase 1; D008239:Lysine
keywords: H3K9 acetylation; H4K12 acetylation; development; epigenetics; explant culture; histone deacetylase inhibitor (HDAC inhibitor) (HDI); photoreceptor; recoverin; retina; rhodopsin