Genomic organization, promoter region analysis, and chromosome localization of the mouse bcl-x gene.
The bcl-x gene, a bcl-2 family member, is highly regulated during lymphoid development, and its expression modulates apoptosis in lymphoid and other cell populations. Several forms of bcl-x mRNAs with different biologic functions have been described in rodents and humans. In this study, we have determined the organization and promoter region of the mouse bcl-x gene in an effort to understand the molecular basis for the different bcl-x mRNA species identified in tissues. We show that mouse bcl-x maps to the distal mouse chromosome 2 at approximately 89 cM, and exhibits a three-exon structure with an untranslated first exon and a facultative first intron. The coding region of bcl-xL is generated by the juncture of exons II and III through a splicing reaction, whereas bcl-xS is generated by an alternatively utilized donor splice site located within exon II. Analysis of multiple cDNAs and primer extension experiments revealed major transcription initiation sites in brain and thymus within a GC-rich region, with multiple Sp1-binding motifs located upstream of exon I. Another promoter was mapped to a 57-bp region localized upstream of the translation initiation codon by transfection of reporter constructs into FL5.12 and K562 cell lines. The remarkable similarity between the genomic regions of bcl-2 and bcl-x suggests that these genes have evolved from a common ancestral gene or through gene duplication.
Grillot
D A
DA
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
González-García
M
M
Ekhterae
D
D
Duan
L
L
Inohara
N
N
Ohta
S
S
Seldin
M F
MF
Nuñez
G
G
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D005796:Genes; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein