Roles of cofactors and chromatin accessibility in hox protein target specificity
Background: The regulation of specific target genes by transcription factors is central to our understanding of gene network control in developmental and physiological processes yet how target specificity is achieved is still poorly understood. This is well illustrated by the Hox family of transcrip...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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2016
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| Online Access: | http://eprints.um.edu.my/15635/1/%28Ori%29roles_of_cofactor_and_chromatin.pdf |
| _version_ | 1825720708807786496 |
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| author | Beh, C.Y. El-Sharnouby, S. Chatzipli, A. Russell, S. Choo, S.W. White, R. |
| author_facet | Beh, C.Y. El-Sharnouby, S. Chatzipli, A. Russell, S. Choo, S.W. White, R. |
| author_sort | Beh, C.Y. |
| collection | UM |
| description | Background: The regulation of specific target genes by transcription factors is central to our understanding of gene network control in developmental and physiological processes yet how target specificity is achieved is still poorly understood. This is well illustrated by the Hox family of transcription factors as their limited in vitro DNA-binding specificity contrasts with their clear in vivo functional specificity. Results: We generated genome-wide binding profiles for three Hox proteins, Ubx, Abd-A and Abd-B, following transient expression in Drosophila Kc167 cells, revealing clear target specificity and a striking influence of chromatin accessibility. In the absence of the TALE class homeodomain cofactors Exd and Hth, Ubx and Abd-A bind at a very similar set of target sites in accessible chromatin, whereas Abd-B binds at an additional specific set of targets. Provision of Hox cofactors Exd and Hth considerably modifies the Ubx genome-wide binding profile enabling Ubx to bind at an additional novel set of targets. Both the Abd-B specific targets and the cofactor-dependent Ubx targets are in chromatin that is relatively DNase1 inaccessible prior to the expression of Hox proteins/Hox cofactors. Conclusions: Our experiments demonstrate a strong role for chromatin accessibility in Hox protein binding and suggest that Hox protein competition with nucleosomes has a major role in Hox protein target specificity in vivo. |
| first_indexed | 2024-03-06T05:39:15Z |
| format | Article |
| id | um.eprints-15635 |
| institution | Universiti Malaya |
| language | English |
| last_indexed | 2024-03-06T05:39:15Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | um.eprints-156352016-03-01T08:42:44Z http://eprints.um.edu.my/15635/ Roles of cofactors and chromatin accessibility in hox protein target specificity Beh, C.Y. El-Sharnouby, S. Chatzipli, A. Russell, S. Choo, S.W. White, R. RZ Other systems of medicine Background: The regulation of specific target genes by transcription factors is central to our understanding of gene network control in developmental and physiological processes yet how target specificity is achieved is still poorly understood. This is well illustrated by the Hox family of transcription factors as their limited in vitro DNA-binding specificity contrasts with their clear in vivo functional specificity. Results: We generated genome-wide binding profiles for three Hox proteins, Ubx, Abd-A and Abd-B, following transient expression in Drosophila Kc167 cells, revealing clear target specificity and a striking influence of chromatin accessibility. In the absence of the TALE class homeodomain cofactors Exd and Hth, Ubx and Abd-A bind at a very similar set of target sites in accessible chromatin, whereas Abd-B binds at an additional specific set of targets. Provision of Hox cofactors Exd and Hth considerably modifies the Ubx genome-wide binding profile enabling Ubx to bind at an additional novel set of targets. Both the Abd-B specific targets and the cofactor-dependent Ubx targets are in chromatin that is relatively DNase1 inaccessible prior to the expression of Hox proteins/Hox cofactors. Conclusions: Our experiments demonstrate a strong role for chromatin accessibility in Hox protein binding and suggest that Hox protein competition with nucleosomes has a major role in Hox protein target specificity in vivo. 2016 Article PeerReviewed application/pdf en http://eprints.um.edu.my/15635/1/%28Ori%29roles_of_cofactor_and_chromatin.pdf Beh, C.Y. and El-Sharnouby, S. and Chatzipli, A. and Russell, S. and Choo, S.W. and White, R. (2016) Roles of cofactors and chromatin accessibility in hox protein target specificity. Epigenetics and Chromatin, 9 (1). ISSN 1756-8935, DOI https://doi.org/10.1186/s13072-015-0049-x <https://doi.org/10.1186/s13072-015-0049-x>. 10.1186/s13072-015-0049-x |
| spellingShingle | RZ Other systems of medicine Beh, C.Y. El-Sharnouby, S. Chatzipli, A. Russell, S. Choo, S.W. White, R. Roles of cofactors and chromatin accessibility in hox protein target specificity |
| title | Roles of cofactors and chromatin accessibility in hox protein target specificity |
| title_full | Roles of cofactors and chromatin accessibility in hox protein target specificity |
| title_fullStr | Roles of cofactors and chromatin accessibility in hox protein target specificity |
| title_full_unstemmed | Roles of cofactors and chromatin accessibility in hox protein target specificity |
| title_short | Roles of cofactors and chromatin accessibility in hox protein target specificity |
| title_sort | roles of cofactors and chromatin accessibility in hox protein target specificity |
| topic | RZ Other systems of medicine |
| url | http://eprints.um.edu.my/15635/1/%28Ori%29roles_of_cofactor_and_chromatin.pdf |
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