High Mobility Group I Proteins Interfere with the Homeodomains Binding to DNA

Homeodomains (HDs) constitute the DNA binding domain of several transcription factors that control cell differentiation and development in a wide variety of organisms. Most HDs recognize sequences that contain a 5′-TAAT-3′ core motif. However, the DNA binding specificity of HD-containing proteins do...

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Bibliographic Details
Published in:	The Journal of biological chemistry 1997-11, Vol.272 (47), p.29904-29910
Main Authors:	Arlotta, Paola, Rustighi, Alessandra, Mantovani, Fiamma, Manfioletti, Guidalberto, Giancotti, Vincenzo, Tell, Gianluca, Damante, Giuseppe
Format:	Article
Language:	eng
Subjects:	3T3 Cells Animals Binding Sites Binding, Competitive DNA - metabolism DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism High Mobility Group Proteins - genetics High Mobility Group Proteins - metabolism HMGA1a Protein Homeodomain Proteins - metabolism Mice Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Transcriptional Activation Transfection
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Summary:	Homeodomains (HDs) constitute the DNA binding domain of several transcription factors that control cell differentiation and development in a wide variety of organisms. Most HDs recognize sequences that contain a 5′-TAAT-3′ core motif. However, the DNA binding specificity of HD-containing proteins does not solely determine their biological effects, and other molecular mechanisms should be responsible for their ultimate functional activity. Interference by other factors in the HD/DNA interaction could be one of the processes by which HD-containing proteins achieve the functional complexity required for their effects on the expression of target genes. Using gel-retardation assay, we demonstrate that two members of the high mobility group I (HMGI) family of nuclear proteins (HMGI-C and HMGY) can bind to a subset of HD target sequences and inhibit HDs from binding to the same sequences. The inhibition of the HD/DNA interaction occurs while incubating HMGI-C with DNA either before or after the addition of the HD. The reduced half-life of the HD·DNA complex in the presence of HMGI-C, and the shift observed in the CD spectra recorded upon HMGI-C binding to DNA, strongly suggest that structural modifications of the DNA are responsible for the inhibition of the HD·DNA complex formation. Moreover, by co-transfection experiments we provide evidence that this inhibition can occur also in vivo. The data reported here would suggest that HMGI proteins may be potential regulators of the function of HD-containing proteins and that they are able to interfere with the access of the HD to their target genes.
ISSN:	0021-9258 1083-351X