During the differentiation of adipocytes, or any other cell type, dramatic alterations occur in gene expression. Transcription factors that bind specific DNA sequences in the regulatory regions of genes, play a critical role in directing their activity. Of the many classes of transcription factors identified to date, members of the HOX gene family of transcription factors are among the most well characterized group. It is the goal of the applicant to more fully understand early adipocyte development and to define the role that HOX proteins play in early stages of fat cell differentiation. The applicant has identified at least two HOX gene products that are differentially expressed during early stages of differentiation. The goal of the proposal is to utilize 3T3-L1 and rat preadipocytes in primary culture to functionally define the role of HOX proteins by examining gain and loss of functions in cells where HOX proteins have been overexpressed or suppressed by antisense. In addition, the applicant proposes to identify the target nucleotide sequences to which homeobox transcription factors bind, and identify HOX genes expressed very early in adipocyte differentiation.
