ABSTRACT
INTRODUCTION While many proteins with functions related to metabolism, structure or gene expression are present in the majority of the cells of a differentiated organism, the unique functions of specific cell types depend on the exclusive expression of particular genes. Immunoglobulins are expressed by B lymphocytes, myosin preferentially by muscle cells, α-crystallin by cells of the ocular lens. Many different mechanisms can be conceived that might account for the establishment of such cell type specific protein expression during embryogenesis and development, and its maintainance in the differentiated cell. Genes may become altered during lineage determination or differentiation, for example by methylation or alteration of the chromatin structure, affecting accessibility of the DNA by transcription factors. Regulatory chain reactions, instigated by environmental cues, could lead to synthesis of activators or repressers that may ultimately modulate transcription and translation. These mechanisms require cis-reponsive elements, which are positioned in the coding, intronic, or flanking sequences of the genes, and are often targets of trans-acting factors. The limiting complexity of the genome requires the postulation of "combinatorial" gene regulation, whereby the interplay of different widely expressed regulatory proteins creates spatial and temporal specificity (Ernst and Smale, 1995). There is now a wealth of information about these regulatory phenomena, and the technology is in place to expand this knowledge: analyses of chromatin structure and transcript boundaries help to localize cis-responsive elements, transgenes reveal their inclusion or loss in the cloning process, and DNAse protections and gelshifts identify and define trans-acting factors. However, it is probably fair to state that we presently lack a complete understanding of the exact regulation of most genes.
