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Publication : ZBED4, a BED-type zinc-finger protein in the cones of the human retina.

First Author  Saghizadeh M Year  2009
Journal  Invest Ophthalmol Vis Sci Volume  50
Issue  8 Pages  3580-8
PubMed ID  19369242 Mgi Jnum  J:154557
Mgi Id  MGI:4397541 Doi  10.1167/iovs.08-2751
Citation  Saghizadeh M, et al. (2009) ZBED4, a BED-type zinc-finger protein in the cones of the human retina. Invest Ophthalmol Vis Sci 50(8):3580-8
abstractText  PURPOSE: To characterize the ZBED4 cDNA identified by subtractive hybridization and microarray of retinal cone degeneration (cd) adult dog mRNA from mRNA of normal dog retina. METHODS: The cDNA library obtained from subtractive hybridization was arrayed and screened with labeled amplicons from normal and cd dog retinas. Northern blot analysis was used to verify ZBED4 mRNA expression in human retina. Flow cytometry sorted peanut agglutinin (PNA)-labeled cones from dissociated mouse retinas, and quantitative RT-PCR (QPCR) was used to measure ZBED4 mRNA levels in these cone cells. Immunohistochemistry localized ZBED4 in human retinas. Expression of ZBED4 mRNA transiently transfected into HEK293 cells was analyzed by immunofluorescence. ZBED4 subcellular localization was determined with Western blot analysis. RESULTS: One of 80 cDNAs differentially expressed in normal and cd dog retinas corresponded to a novel gene, ZBED4, which is also expressed in human and mouse retinas. ZBED4 mRNA was found to be present in cone photoreceptors. When ZBED4 cDNA was transfected into HEK293 cells, the expressed protein showed nuclear localization. However, in human retinas, ZBED4 was localized to cone nuclei, inner segments, and pedicles, as well as to Muller cell endfeet. Confirming these immunohistochemical results, the 135-kDa ZBED4 was found in both the nuclear and cytosolic extracts of human retinas. ZBED4 has four predicted DNA-binding domains, a dimerization domain, and two LXXLL motifs characteristic of coactivators/corepressors of nuclear hormone receptors. CONCLUSIONS: ZBED4 cellular/subcellular localization and domains suggest a regulatory role for this protein, which may exert its effects in cones and Muller cells through multiple ways of action.
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