Point mutations within AT-hook domains of the HMGI homologue HMGIYL1 affect binding to gene promoter but not to four-way junction DNA

Citation
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
Citations number
66
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMISTRY
ISSN journal
00062960 → ACNP
Volume
39
Issue
47
Year of publication
2000
Pages
14419 - 14425
Database
ISI
SICI code
0006-2960(20001128)39:47<14419:PMWADO>2.0.ZU;2-H
Abstract
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.