Genomic organization of human MXI1, a putative tumor suppressor gene.

MXI1, a member of the MYC family of transcription factors, is thought to negatively regulate MYC function and may therefore be a potential tumor suppressor gene. Using detailed restriction mapping and partial DNA sequencing analysis, we have determined the genomic organization of the human MXI1 gene to facilitate a search for mutations that affect MXI1 function. The gene spans a region of approximately 60 kb on chromosome 10q24-q25 and comprises six exons. The correspondence of these exons to previously identified Mxi1 functional domains suggests that alternatively spliced transcripts may regulate Mxi1 functional activity. The presence of a cryptic ATG start codon in exon 2 suggests that a functional protein missing the SIN3-interacting domain (exon 1) may be generated by alternative splicing. Finally, we have identified two polymorphic regions within the MXI1 locus: a polymorphic CA repeat in the third intron and an AAAAC polymorphism in the noncoding region of exon 6. These findings will facilitate the analysis of tumors for the presence of inactivating mutations in MXI1 coding and regulatory sequences.