Functional Specificity of a Hox Protein Mediated by the Recognition of Minor Groove Structure Export

@article{citeulike:1853316, abstract = {Summary The recognition of specific DNA-binding sites by transcription factors is a critical yet poorly understood step in the control of gene expression. Members of the Hox family of transcription factors bind DNA by making nearly identical major groove contacts via the recognition helices of their homeodomains. In vivo specificity, however, often depends on extended and unstructured regions that link Hox homeodomains to a DNA-bound cofactor, Extradenticle (Exd). Using a combination of structure determination, computational analysis, and in vitro and in vivo assays, we show that Hox proteins recognize specific Hox-Exd binding sites via residues located in these extended regions that insert into the minor groove but only when presented with the correct DNA sequence. Our results suggest that these residues, which are conserved in a paralog-specific manner, confer specificity by recognizing a sequence-dependent DNA structure instead of directly reading a specific DNA sequence.}, author = {Joshi, Rohit and Passner, Jonathan M. and Rohs, Remo and Jain, Rinku and Sosinsky, Alona and Crickmore, Michael A. and Jacob, Vinitha and Aggarwal, Aneel K. and Honig, Barry and Mann, Richard S.}, citeulike-article-id = {1853316}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cell.2007.09.024}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0092867407012123}, citeulike-linkout-2 = {http://www.sciencedirect.com/science/article/B6WSN-4R1NGP6-K/2/947984bb8dcfc0c81a4d1e1fb146f593}, comment = {Very interesting article that shows that target specificity of Hox-Exd depends on both major and minor groove contacts. Major groove contact patterns seem to be common to all Hox proteins, and allow them to bind to A/T rich sequences. The minor groove interaction may allow certain Hox proteins to specifically target certain sites. Interestingly, what created the minor groove interaction is a narrow minor groove, that in turn creates an elevated electrostatic potential that favors binding of basic residues. The authors seem to think that minor groove contacts might be more widespread than previously thought.}, day = {02}, doi = {10.1016/j.cell.2007.09.024}, issn = {00928674}, journal = {Cell}, keywords = {code, columbia, structure, transcription\_factor}, month = {November}, number = {3}, pages = {530--543}, posted-at = {2007-11-01 22:39:00}, priority = {0}, title = {Functional Specificity of a Hox Protein Mediated by the Recognition of Minor Groove Structure}, url = {http://dx.doi.org/10.1016/j.cell.2007.09.024}, volume = {131}, year = {2007} }

TY - JOUR ID - citeulike:1853316 L3 - citeulike-article-id:1853316 N2 - Summary The recognition of specific DNA-binding sites by transcription factors is a critical yet poorly understood step in the control of gene expression. Members of the Hox family of transcription factors bind DNA by making nearly identical major groove contacts via the recognition helices of their homeodomains. In vivo specificity, however, often depends on extended and unstructured regions that link Hox homeodomains to a DNA-bound cofactor, Extradenticle (Exd). Using a combination of structure determination, computational analysis, and in vitro and in vivo assays, we show that Hox proteins recognize specific Hox-Exd binding sites via residues located in these extended regions that insert into the minor groove but only when presented with the correct DNA sequence. Our results suggest that these residues, which are conserved in a paralog-specific manner, confer specificity by recognizing a sequence-dependent DNA structure instead of directly reading a specific DNA sequence. IS - 3 JF - Cell SN - 00928674 EP - 543 TI - Functional Specificity of a Hox Protein Mediated by the Recognition of Minor Groove Structure VL - 131 SP - 530 KW - code KW - columbia KW - structure KW - transcription_factor N1 - Very interesting article that shows that target specificity of Hox-Exd depends on both major and minor groove contacts. Major groove contact patterns seem to be common to all Hox proteins, and allow them to bind to A/T rich sequences. The minor groove interaction may allow certain Hox proteins to specifically target certain sites. Interestingly, what created the minor groove interaction is a narrow minor groove, that in turn creates an elevated electrostatic potential that favors binding of basic residues. The authors seem to think that minor groove contacts might be more widespread than previously thought. AU - Joshi, Rohit AU - Passner, Jonathan AU - Rohs, Remo AU - Jain, Rinku AU - Sosinsky, Alona AU - Crickmore, Michael AU - Jacob, Vinitha AU - Aggarwal, Aneel AU - Honig, Barry AU - Mann, Richard PY - 2007/11/02/ UR - http://dx.doi.org/10.1016/j.cell.2007.09.024 ER -