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The Sp family of transcription factors
G-rich elements such as GC- (GGGGCGGGG) and GT/CACC-boxes (GGTGTGGGG) are important cis-acting elements required
for the appropriate expression of housekeeping as well as many tissue-specific and viral genes. These motifs have
been found and functionally analyzed in promoters, enhancers and locus control regions of genes that are under
different modes of control such as cell cycle regulation, hormonal activation and developmental patterning.
For long it is known that the general transcription factor Sp1 (named according to the original purification scheme
that included Sephacryl and phosphocellulose columns) can bind and act through GC/GT-boxes, and Sp1 was therefore
thought to be an extremely versatile protein essential for many different functions of the mammalian nucleus.
However, Sp1 is not the only transcription factor binding and acting through these elements. It simply represents
the first identified and cloned protein of the Sp/XKLF family of transcription factors. Family members contain a
highly conserved DNA-binding domain consisting of three zinc fingers. Currently this family of transcription factors
comprises at least 25 different mammalian members including the Sp1-related, but distinct, factors Sp2, Sp3 and Sp4.
The identification of all these transcription factors binding to GC/GT-boxes raises questions that are central to our work:
- What are the functions of these proteins in vivo?
- What determines their specificity?
- How are they regulated?
Funded by Deutsche Forschungsgemeinschaft (DFG)
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