title: A conserved sequence upstream of the B29 (Ig beta, CD79b) gene interacts with YY1.
abstract: The human, murine, and rat B29 (Ig beta, CD79b) genes are highly conserved in sequence and organization and exhibit strict B cell-specific expression. In the human and rat genomes, the B29 gene is located between the skeletal muscle-specific Na-channel alpha subunit (SCN4A) gene and the pituitary-specific growth hormone (GH-N) gene. The human pituitary-specific GH-N gene is controlled by a tissue-specific locus control region (LCR) located just upstream of the B29 promoter that mediates tissue-specific enhancement, histone acetylation, and an open chromatin conformation across the B29 gene in growth hormone (GH)-expressing pituitary cells. Here we show that B29 mRNA is not detected in a GH-expressing pituitary cell line and that GH-N mRNA is not detected in B cells. This differential expression suggests that the B29 gene is insulated or otherwise protected from the regulatory influences of the closely proximal GH LCR. We searched available sequences upstream of the human, mouse, and rat B29 genes and found a highly conserved sequence that fulfills the criteria recently established for non-coding DNA elements potentially involved in gene control. This B29 conserved sequence (BCS) bound ubiquitously expressed nuclear protein complexes. DNase I protection analysis of the BCS revealed a central 'footprinted' core which was confirmed to bind the multifunctional transcription factor, YY1. However, neither the BCS nor the YY1-binding core motif exhibited silencer or enhancer activity in transient transfections or position-independent insulator activity in enhancer-blocking assays. Thus, the BCS may function as a tissue-specific LCR or position-dependent insulator specifically countering the influences of the 5' GH LCR and controlling B29 gene expression.
authors.affiliation: Department of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Patrone
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Henson
authors.forename: Randolph
authors.initials: R
authors.lastname: Wall
authors.forename: Cindy Sue
authors.initials: CS
authors.lastname: Malone
mesh_terms: D024506:5' Flanking Region; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001402:B-Lymphocytes / Q000502:physiology; D001483:Base Sequence; D001665:Binding Sites; D051925:CD79 Antigens; D002460:Cell Line; D017124:Conserved Sequence; D003850:Deoxyribonuclease I / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D050981:Erythroid-Specific DNA-Binding Factors; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019901:Locus Control Region; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D037941:Silencer Elements, Transcriptional; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050986:YY1 Transcription Factor
chemical_list: D015703:Antigens, CD; D051925:CD79 Antigens; C497883:CD79B protein, human; C497884:Cd79b protein, mouse; C497885:Cd79b protein, rat; D050981:Erythroid-Specific DNA-Binding Factors; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C494699:Yy1 protein, mouse; C494700:Yy1 protein, rat; D013006:Growth Hormone; D003850:Deoxyribonuclease I