Members of the MEIS1 homeoprotein family are involved in binding the laminin B1 enhancer
Homeoboxes are a diverse class of regulatory genes that share a common DNA binding motif, termed the homeodomain, and are known to play integral roles in normal and neoplastic development. The Meis1 ( Myeloid ecotropic viral integration site 1) homeobox gene was identified as a common site of retroviral integration in BXH-2 mice, which serve as a model system for identifying genes involved in myeloid leukemia. Southern blot analysis suggested that Meis1 is a member of a well conserved multigene family. The first goal of this work was to identify and characterize Meis1-related genes. Screening of a cDNA library led to the isolation of Mrg1 (Meis1- related gene 1). The open reading frames of Meis1 and Mrg1 were found to be highly similar with nearly identical homeodomains. Coupled with database searching for additional sequences with homology to the Meis1 homeodomain, these studies led to the identification of the MEIS1 homeobox family, which is highly conserved throughout evolution. The second goal of this work was to further characterize the function(s) of MEIS1 family proteins by identifying a cellular promoter/enhancer element bound by a MEIS1 complex. Through the use of electrophoretic mobility shift assays, it was determined that multiple MEIS1 family proteins complex with members of the Pbx family of homeoproteins to bind an element contained within the 5[special characters omitted] regulatory region of the Laminin [special characters omitted]1 (Lamb1-1) gene. Additionally, multiple MEIS1 proteins were found to be upregulated following retinoic acid treatment with kinetics consistent with maximal Lamb1-1 activation. This is an interesting finding, since Laminin is known to be involved in the growth and development of both normal and neoplastic cells. Regulation of Lamb1-1 may therefore serve as a mechanism by which MEIS1 proteins are involved in normal and neoplastic development.
Steelman, Scott, "Members of the MEIS1 homeoprotein family are involved in binding the laminin B1 enhancer" (1999). ProQuest ETD Collection - Thomas Jefferson University. AAI9923251.