TY - JOUR
T1 - Characterization of human retinal fascin gene (FSCN2) at 17q25
T2 - Close physical linkage of fascin and cytoplasmic actin genes
AU - Tubb, Benjamin E.
AU - Bardien-Kruger, Soraya
AU - Kashork, Catherine D.
AU - Shaffer, Lisa G.
AU - Ramagli, Louis S.
AU - Xu, Jingping
AU - Siciliano, Michael J.
AU - Bryan, Joseph
N1 - Funding Information:
We thank Jeremy Nathans at Johns Hopkins Medical School for sharing the human retinal cDNA library; Wei He at the Baylor College of Medicine (BCM) Department of Biochemistry for help with Northern blots; Yi-Mieng Chang at the BCM Cloning Core Laboratory for performing the BAC library screens; and Nidhi Sharma and Lydia Aguilar-Bryan at the BCM Department of Endocrinology for help with SSCP. B.T. is funded as a Hudson scholar in the Baylor College of Medicine MSTP program. This work was supported by NIH R01 GM26091 to Joseph Bryan.
PY - 2000/4/15
Y1 - 2000/4/15
N2 - Retinal fascin is a newly identified photoreceptor-specific paralog of the actin-bundling protein fascin. Fascins crosslink f-actin into highly ordered bundles within dynamic cell extensions such as neuronal growth cone filopodia. We have isolated cDNA and genomic clones of human retinal fascin and characterized the structure of the human retinal fascin gene (FSCN2). The cDNA predicts a protein of 492 amino acids and molecular mass 55,057 that shows 94% identity to bovine retinal fascin and 56% identity to human fascin. Promoter analysis reveals a consensus retinoic acid response element and several potential binding sites for transcription factors Crx and Nrl, which correlates with the retina-specific expression of FSCN2 mRNA. Fluorescence in situ hybridization analysis and genomic clone sequencing indicate that the FSCN2 gene lies within 266 kb of the actin gene ACTG1 at 17q25. Database searches revealed that the human fascin gene FSCN1 and actin gene ACTB at 7p22 also coexist within a 266-kb genomic clone. The close physical linkage of these fascin/actin gene pairs suggests that they derive from a common gene duplication event and allows comparison of fascin and actin phylogenetic analyses. Finally, a possible link to the retinitis pigmentosa 17 allele (RP17) at distal 17q was excluded by demonstration of multiple independent segregation events in two RP17 kindreds. Informative FSCN2 polymorphisms were identified and will serve as useful markers in future linkage studies. The likely function of retinal fascin, in light of known fascin roles in other cell types, is to assemble actin microfilaments in support of photo-receptor disk morphogenesis. (C) 2000 Academic Press.
AB - Retinal fascin is a newly identified photoreceptor-specific paralog of the actin-bundling protein fascin. Fascins crosslink f-actin into highly ordered bundles within dynamic cell extensions such as neuronal growth cone filopodia. We have isolated cDNA and genomic clones of human retinal fascin and characterized the structure of the human retinal fascin gene (FSCN2). The cDNA predicts a protein of 492 amino acids and molecular mass 55,057 that shows 94% identity to bovine retinal fascin and 56% identity to human fascin. Promoter analysis reveals a consensus retinoic acid response element and several potential binding sites for transcription factors Crx and Nrl, which correlates with the retina-specific expression of FSCN2 mRNA. Fluorescence in situ hybridization analysis and genomic clone sequencing indicate that the FSCN2 gene lies within 266 kb of the actin gene ACTG1 at 17q25. Database searches revealed that the human fascin gene FSCN1 and actin gene ACTB at 7p22 also coexist within a 266-kb genomic clone. The close physical linkage of these fascin/actin gene pairs suggests that they derive from a common gene duplication event and allows comparison of fascin and actin phylogenetic analyses. Finally, a possible link to the retinitis pigmentosa 17 allele (RP17) at distal 17q was excluded by demonstration of multiple independent segregation events in two RP17 kindreds. Informative FSCN2 polymorphisms were identified and will serve as useful markers in future linkage studies. The likely function of retinal fascin, in light of known fascin roles in other cell types, is to assemble actin microfilaments in support of photo-receptor disk morphogenesis. (C) 2000 Academic Press.
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U2 - 10.1006/geno.2000.6156
DO - 10.1006/geno.2000.6156
M3 - Article
C2 - 10783262
AN - SCOPUS:0034655939
SN - 0888-7543
VL - 65
SP - 146
EP - 156
JO - Genomics
JF - Genomics
IS - 2
ER -