A signature motif mediating selective interactions of BCL11A with the NR2E/F subfamily of orphan nuclear receptors
Despite their physiological importance, selective interactions between nuclear receptors (NRs) and their cofactors are poorly understood. Here, we describe a novel signature motif (F/YSXXLXXL/Y) in the developmental regulator BCL11A that facilitates its selective interaction with members of the NR2E...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
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Oxford University Press
2013
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| Online Access: | https://eprints.nottingham.ac.uk/29027/ |
| _version_ | 1848793700000333824 |
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| author | Chan, Chun Ming Fulton, Joel Montiel-Duarte, Cristina Collins, Hilary M. Bharti, Neetu Wadelin, Frances R. Moran, Paula M. Mongan, Nigel P. Heery, David M. |
| author_facet | Chan, Chun Ming Fulton, Joel Montiel-Duarte, Cristina Collins, Hilary M. Bharti, Neetu Wadelin, Frances R. Moran, Paula M. Mongan, Nigel P. Heery, David M. |
| author_sort | Chan, Chun Ming |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Despite their physiological importance, selective interactions between nuclear receptors (NRs) and their cofactors are poorly understood. Here, we describe a novel signature motif (F/YSXXLXXL/Y) in the developmental regulator BCL11A that facilitates its selective interaction with members of the NR2E/F subfamily. Two copies of this motif (named here as RID1 and RID2) permit BCL11A to bind COUP-TFs (NR2F1;NR2F2;NR2F6) and Tailless/TLX (NR2E1), whereas RID1, but not RID2, binds PNR (NR2E3). We confirmed the existence of endogenous BCL11A/TLX complexes in mouse cortex tissue. No interactions of RID1 and RID2 with 20 other ligand-binding domains from different NR subtypes were observed. We show that RID1 and RID2 are required for BCL11A-mediated repression of endogenous γ-globin gene and the regulatory non-coding transcript Bgl3, and we identify COUP-TFII binding sites within the Bgl3 locus. In addition to their importance for BCL11A function, we show that F/YSXXLXXL/Y motifs are conserved in other NR cofactors. A single FSXXLXXL motif in the NR-binding SET domain protein NSD1 facilitates its interactions with the NR2E/F subfamily. However, the NSD1 motif incorporates features of both LXXLL and FSXXLXXL motifs, giving it a distinct NR-binding pattern in contrast to other cofactors. In summary, our results provide new insights into the selectivity of NR/cofactor complex formation. |
| first_indexed | 2025-11-14T19:04:27Z |
| format | Article |
| id | nottingham-29027 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:04:27Z |
| publishDate | 2013 |
| publisher | Oxford University Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-290272020-05-04T20:18:33Z https://eprints.nottingham.ac.uk/29027/ A signature motif mediating selective interactions of BCL11A with the NR2E/F subfamily of orphan nuclear receptors Chan, Chun Ming Fulton, Joel Montiel-Duarte, Cristina Collins, Hilary M. Bharti, Neetu Wadelin, Frances R. Moran, Paula M. Mongan, Nigel P. Heery, David M. Despite their physiological importance, selective interactions between nuclear receptors (NRs) and their cofactors are poorly understood. Here, we describe a novel signature motif (F/YSXXLXXL/Y) in the developmental regulator BCL11A that facilitates its selective interaction with members of the NR2E/F subfamily. Two copies of this motif (named here as RID1 and RID2) permit BCL11A to bind COUP-TFs (NR2F1;NR2F2;NR2F6) and Tailless/TLX (NR2E1), whereas RID1, but not RID2, binds PNR (NR2E3). We confirmed the existence of endogenous BCL11A/TLX complexes in mouse cortex tissue. No interactions of RID1 and RID2 with 20 other ligand-binding domains from different NR subtypes were observed. We show that RID1 and RID2 are required for BCL11A-mediated repression of endogenous γ-globin gene and the regulatory non-coding transcript Bgl3, and we identify COUP-TFII binding sites within the Bgl3 locus. In addition to their importance for BCL11A function, we show that F/YSXXLXXL/Y motifs are conserved in other NR cofactors. A single FSXXLXXL motif in the NR-binding SET domain protein NSD1 facilitates its interactions with the NR2E/F subfamily. However, the NSD1 motif incorporates features of both LXXLL and FSXXLXXL motifs, giving it a distinct NR-binding pattern in contrast to other cofactors. In summary, our results provide new insights into the selectivity of NR/cofactor complex formation. Oxford University Press 2013-11 Article PeerReviewed Chan, Chun Ming, Fulton, Joel, Montiel-Duarte, Cristina, Collins, Hilary M., Bharti, Neetu, Wadelin, Frances R., Moran, Paula M., Mongan, Nigel P. and Heery, David M. (2013) A signature motif mediating selective interactions of BCL11A with the NR2E/F subfamily of orphan nuclear receptors. Nucleic Acids Research, 41 (21). pp. 9663-9679. ISSN 1362-4962 http://nar.oxfordjournals.org/content/41/21/9663 doi:10.1093/nar/gkt761 doi:10.1093/nar/gkt761 |
| spellingShingle | Chan, Chun Ming Fulton, Joel Montiel-Duarte, Cristina Collins, Hilary M. Bharti, Neetu Wadelin, Frances R. Moran, Paula M. Mongan, Nigel P. Heery, David M. A signature motif mediating selective interactions of BCL11A with the NR2E/F subfamily of orphan nuclear receptors |
| title | A signature motif mediating selective interactions of BCL11A with the NR2E/F subfamily of orphan nuclear receptors |
| title_full | A signature motif mediating selective interactions of BCL11A with the NR2E/F subfamily of orphan nuclear receptors |
| title_fullStr | A signature motif mediating selective interactions of BCL11A with the NR2E/F subfamily of orphan nuclear receptors |
| title_full_unstemmed | A signature motif mediating selective interactions of BCL11A with the NR2E/F subfamily of orphan nuclear receptors |
| title_short | A signature motif mediating selective interactions of BCL11A with the NR2E/F subfamily of orphan nuclear receptors |
| title_sort | signature motif mediating selective interactions of bcl11a with the nr2e/f subfamily of orphan nuclear receptors |
| url | https://eprints.nottingham.ac.uk/29027/ https://eprints.nottingham.ac.uk/29027/ https://eprints.nottingham.ac.uk/29027/ |