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Repeated Sequences of Regulating Gene Expression -

In a strict sense, some of the control sequences just described is really repeated sequences. Short elements, such as the TATA or CAAT boxes, appear in many promoters and hence are repeated, but because they are so short are not recognized in hybridization experiments.

Enhancers may sometimes contain several repeats of a somewhat longer sequence (such as the 72-nucleotide repeats of the SV40 enhancer), By themselves, however, these do not reach sufficiently high copy numbers to be detected in classical reassociation experiments and no extensive sequence homology exists among enhancers as a class, although some short homologies have been found. Therefore, none of the gene regulatory elements discussed thus far can be considered "classical" repeated sequences.

Evidence for the involvement of "classical" repeated sequences in gene regulation is far more circumstantial and is based on the occurrence of repeat sequence transcripts in the RNA population. Although most mRNAs are transcripts of single copy genes, repeat transcripts can often be found when Cloned repeat sequence probes are used to increase sensitivity. This is especially true in nuclear RNAs, wherein the RNA contains transcripts of many interspersed repeat sequences.

When different stages of develop­ment are compared, it is usually found that the repeat sequences which are most abundant in RNA differ from stage to stage. Of course, simply because repetitive sequences are transcribed, or because their transcription changes during development, does not prove that they are involved in gene regulation. It seems likely that most transcribed repeats are simply sequence elements that have found their way into transcription units by evolutionary accidents or rearrangement or transposition.

On the other hand, if must be admitted that a small class of functionally important repeat sequences might exist against a large background of evolutionary noise. Several lines of evidence from animal systems suggest that this may be true.

The transcriptional elements are parts of a gene or its flanking sequences and affect only the gene to which they are directly linked. In genetic terms they function cis, regulating genes on the same chromosome. Clearly, there must be other elements involved in gene regulation and, as a matter of fact, there is now good experimental evidence that in some cases certain protein factors must be bound to specific sites in a gene or its flanking sequences in order to initiate transcription.

An example is the transcription factor which binds to the heat shock promoter in Drosophila. Genes encod­ing this factor would be examples of trans-acting control elements. As their name implies, such elements are capable of affecting genes other than those located on the same chromosome. Transacting regulatory genes are well known from genetic studies but our understanding of the molecular nature of such elements, and the factors which presumably mediate their effects, is still quite limited. Certainly, their importance can hardly be denied.