Regulation of alphaA-crystallin via Pax6, c-Maf, CREB and a broad domain of lens-specific chromatin

Autor: Anping Li, Ana B. Chepelinsky, Kongming Wu, Arthur I. Skoultchi, Bharesh K. Chauhan, Nady Golestaneh, Melinda K. Duncan, Chun Y. Gao, Yan Wang, Ales Cvekl, Richard G. Pestell, K. Cveklova, Ying Yang, Tomas Stopka
Rok vydání: 2005
Předmět:
PAX6 Transcription Factor
Transcription
Genetic
Chromosomal Proteins
Non-Histone
Molecular Sequence Data
Alpha-Crystallin A Chain
Mice
Transgenic
CREB
alpha-Crystallin A Chain
General Biochemistry
Genetics and Molecular Biology
Chromatin remodeling
Article
Histones
Tissue Culture Techniques
Mice
Crystallin
Genes
Reporter
Lens
Crystalline
Animals
Humans
Paired Box Transcription Factors
Amino Acid Sequence
Cyclic AMP Response Element-Binding Protein
Eye Proteins
Promoter Regions
Genetic
Molecular Biology
Adenosine Triphosphatases
Homeodomain Proteins
Reporter gene
General Immunology and Microbiology
biology
General Neuroscience
DNA Helicases
Gene Expression Regulation
Developmental
Nuclear Proteins
Cell Differentiation
Molecular biology
Lens Fiber
eye diseases
Chromatin
Repressor Proteins
Proto-Oncogene Proteins c-maf
biology.protein
Lens fiber cell differentiation
sense organs
RNA Polymerase II
Protein Binding
Signal Transduction
Transcription Factors
Zdroj: The EMBO journal. 25(10)
ISSN: 0261-4189
Popis: Pax6 and c-Maf regulate multiple stages of mammalian lens development. Here, we identified novel distal control regions (DCRs) of the alphaA-crystallin gene, a marker of lens fiber cell differentiation induced by FGF-signaling. DCR1 stimulated reporter gene expression in primary lens explants treated with FGF2 linking FGF-signaling with alphaA-crystallin synthesis. A DCR1/alphaA-crystallin promoter (including DCR2) coupled with EGFP virtually recapitulated the expression pattern of alphaA-crystallin in lens epithelium and fibers. In contrast, the DCR3/alphaA/EGFP reporter was expressed only in 'late' lens fibers. Chromatin immunoprecipitations showed binding of Pax6 to DCR1 and the alphaA-crystallin promoter in lens chromatin and demonstrated that high levels of alphaA-crystallin expression correlate with increased binding of c-Maf and CREB to the promoter and of CREB to DCR3, a broad domain of histone H3K9-hyperacetylation extending from DCR1 to DCR3, and increased abundance of chromatin remodeling enzymes Brg1 and Snf2h at the alphaA-crystallin locus. Our data demonstrate a novel mechanism of Pax6, c-Maf and CREB function, through regulation of chromatin-remodeling enzymes, and suggest a multistage model for the activation of alphaA-crystallin during lens differentiation.
Databáze: OpenAIRE
Externí odkaz: