Welcome W. Bender
The bithorax complex in the fruit fly is a cluster of “homeotic” genes which confer distinct identities on the different segments of the fly. The genes are strikingly aligned on the DNA in the order of the segments they affect. Many of the interactions of bithorax mutations are difficult to explain with the known forms of transcriptional regulation. The paradoxes hopefully reflect novel molecular mechanisms.
The segments of a fly are “numbered” by genes which appear in stripes in the early embryo; these stripes turn on the homeotic genes in the proper positions. After a few hours, the striped gene products disappear, but cells must remember their segmental address. Memory is conferred by a gene called Polycomb. In Polycomb mutants, the homeotic genes turn on everywhere when the stripes fade. Polycomb keeps the homeotic genes appropriately repressed, most likely by altering the chromatin structure.
We have mapped sites to which Polycomb binds, and we have shown that DNA regions repressed by Polycomb are less accessible in-vivo to various DNA binding proteins. We have deleted these sites; the resulting flies have dramatic segmental transformations consistent with the loss of Polycomb repression.
The bithorax complex, spanning over 300 kb, includes only four protein-coding genes. However, there are many non-coding transcripts throughout the complex. Two of these encode miRNAs which repress expression of the homeotic proteins. We are refining the maps of additional non-coding RNAs, and generating mutations to reveal their functions.
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