title: BP1, a homeodomain-containing isoform of DLX4, represses the beta-globin gene.
abstract: In earlier studies we identified a putative repressor of the human beta-globin gene, termed beta protein 1 (BP1), which binds to two silencer DNA sequences upstream of the adult human beta-globin gene and to a negative control region upstream of the adult delta-globin gene. Further studies demonstrated an inverse correlation between the binding affinity of the BP1 protein for the distal beta-globin silencer sequence and the severity of sickle cell anemia, suggesting a possible role for BP1 in determining the production of hemoglobin S. We have now cloned a cDNA expressing the BP1 protein. Sequencing revealed that BP1 is a member of the homeobox gene family and belongs to the subfamily called Distal-less (DLX), genes important in early development. Further analysis showed that BP1 is an isoform of DLX4. BP1 protein has repressor function towards the beta-globin promoter, acting through the two beta-globin DNA silencers, demonstrated in transient transfection assays. Strong BP1 expression is restricted to placenta and kidney tissue, with no expression in 48 other human tissues. BP1 exhibits regulated expression in the human erythroid cell line MB-02, where its expression decreases upon induction of the beta-globin gene. BP1 is thus the first member of the DLX family with known DNA binding sites and a function in globin gene regulation.
authors.affiliation: Division of Human Genetics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chase
authors.forename: Sidong
authors.initials: S
authors.lastname: Fu
authors.forename: Susanne B
authors.initials: SB
authors.lastname: Haga
authors.forename: Gregory
authors.initials: G
authors.lastname: Davenport
authors.forename: Holly
authors.initials: H
authors.lastname: Stevenson
authors.forename: Khanh
authors.initials: K
authors.lastname: Do
authors.forename: Doris
authors.initials: D
authors.lastname: Morgan
authors.forename: Alex L
authors.initials: AL
authors.lastname: Mah
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Berg
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D015513:Oncogene Proteins; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014157:Transcription Factors
chemical_list: C105304:DLX4 protein, human; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D015513:Oncogene Proteins; D020033:Protein Isoforms; D012097:Repressor Proteins; D014157:Transcription Factors; D005914:Globins