A PAR domain transcription factor is involved in the expression from a hematopoietic-specific promoter for the human LMO2 gene.
The transcription factor LMO2 is believed to exert its effect through the formation of protein-protein interactions with other DNA-binding factors such as GATA-1 and TAL1. Although LMO2 has been shown to be critical for the formation of the erythroid cell lineage, the gene is also expressed in a number of nonerythroid tissues. In this report, we demonstrate that the more distal of the 2 promoters for the LMO2 gene is highly restricted in its pattern of expression, directing the hematopoietic-specific expression of this gene. Deletion and mutation analyses have identified a critical cis element in the first untranslated exon of the gene. This element is a consensus-binding site for a small family of basic leucine zipper proteins containing a proline and acidic amino acid-rich (PAR) domain. Although all 3 members of this family are produced in erythroid cells, only 2 of these proteins, thyrotroph embryonic factor and hepatic leukemia factor, can activate transcription from this LMO2 promoter element. These findings represent a novel mechanism in erythroid gene regulation because PAR proteins have not previously been implicated in this process.
Crable
Scott C
SC
Division of Hematology/Oncology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, OH, USA.
Anderson
Kathleen P
KP
D048868:Adaptor Proteins, Signal Transducing; D024342:Amino Acids, Acidic / Q000032:analysis*; D000818:Animals; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000494:pharmacology; D004912:Erythrocytes / Q000737:chemistry; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D060588:LIM Domain Proteins; D016350:Leucine Zippers; D008099:Liver / Q000737:chemistry / Q000196:embryology; D008667:Metalloproteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011392:Proline / Q000032:analysis*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; D024342:Amino Acids, Acidic; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C490671:HLF protein, human; C490670:Hlf protein, mouse; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; C513188:Lmo2 protein, mouse; D008667:Metalloproteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C489490:TEF protein, human; C489491:Tef protein, mouse; D014157:Transcription Factors; D011392:Proline