Expression of MXI1, a Myc antagonist, is regulated by Sp1 and AP2.
MXI1, a member of the MAD family of Myc antagonists, encodes a transcription factor whose expression must be tightly regulated to maintain normal cell growth and differentiation. To more closely investigate the transcriptional regulation of the human MXI1 gene, we have cloned and characterized the MXI1 promoter. After clarification of the 5'- and 3'-untranslated regions of the cDNA (indicating that the true length of the MXI1 transcript is 2643 base pairs), we identified two transcription initiation sites. We subsequently isolated the MXI1 promoter, which is GC-rich and lacks a TATA box. Although it contains at least six potential initiator sequences, functional studies indicate the proximal two initiator sequences in combination with nearby Sp1 and MED-1 sites together account for virtually all promoter activity. We also demonstrate that MXI1 promoter activity is repressed by high levels of AP2. These studies provide further insight into the complex regulatory mechanisms governing MXI1 gene expression and its role in cellular differentiation and tumor suppression.
Benson
L Q
LQ
Division of Pediatric Hematology, Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
Coon
M R
MR
Krueger
L M
LM
Han
G C
GC
Sarnaik
A A
AA
Wechsler
D S
DS
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D020014:K562 Cells; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D016329:Sp1 Transcription Factor; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C079440:MXI1 protein, human; C118712:MBD4 protein, human