R. Schwanbeck et al., Point mutations within AT-hook domains of the HMGI homologue HMGIYL1 affect binding to gene promoter but not to four-way junction DNA, BIOCHEM, 39(47), 2000, pp. 14419-14425
High-mobility group I/Y (HMGI/Y) proteins are chromosomal proteins involved
in gene and chromatin regulation. Elevated levels of HMGI/Y proteins were
reported in diverse malignant tumors, and rearrangements of their genes are
casually involved in the development of benign tumors. In humans, the chro
mosomal locus Xp22 has been often found to be affected in diverse benign me
senchymal tumors. Recent studies revealed that this region contains a retro
pseudogene HMGIYL1 which potentially can be activated in a way of "exonizat
ion" upon aberrations involving this region. The coding sequence of the HMG
IY-L1 is highly homologous to the HMGI(Y) gene. On the protein level, both
HMGIYL1 and HMGI differ at few amino acid residues, including their putativ
e DNA-binding domains (DBDs). Here we have approached the question of wheth
er the HMGIYL1 product would be able to adopt a role of HMGI in the context
of binding to gene promoters and chromatin. Comparative binding studies, e
mploying protein footprinting technique, revealed that HMGIYL1 has lost the
ability to bind to the promoter of the interferon beta gene, but retained
its high affinity for the four-way junction DNA. Our results stress the imp
ortance of particular residues within the DBDs for DNA binding and demonstr
ate that tight binding of HMGI/Y proteins to the four-way junction DNA can
be achieved in alternative ways. The binding of HMGIYL1 to four-way junctio
n DNA suggests that activation of the HMGIYL1 gene would yield a protein sh
aring some binding properties with HMG1-box proteins and histone H1. Thus,
the HMGTYL1 could interplay together with these components in chromatin reg
ulation.