The long term goal of our research is to understand the process of development and lineage maturation at the molecular level. The model we have chosen for this analysis is avian erythrocyte maturation. The general question posed in this line of investigations is: how and why are a specific subset of eucaryotic genes induced in one developmental pathway and how is that induction regulated? Broken down into component parts, the more general question can be rephrased more precisely: 1) why are some genes expressed in only a single developmental lineage; 2) what are the cis-acting regulatory sequences which govern that response; 3) what are the trans-acting factors which elicit that response; and 4) how do those factors physically interact with the genetic apparatus to transduce the molecular signals to transcribe a gene? We have cloned fourteen different erythroid-specific (or predominant) genes in order to address these questions. Our goals during the next five years are: 1) to complete structural characterization of a subset of these genes (ALA-SE, band 3 and band 4.1); 2) to examine the cis-acting regulatory sequences of these and two other erythroid genes (histone H5 and epsilon- globin) by transient expression assay in erythroid progenitor cells; 3) to clone the regulatory gene encoding the beta-globin enhancer activating protein (and, as information from goal #2 evolves, to clone other regulatory proteins with other erythroid (and non- erythroid) genes to determine how a tissue-specific transcriptional response is elicited.
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