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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.

Authors

Chun Ming Chan

Joel Fulton

Cristina Montiel-Duarte

Hilary M. Collins

Neetu Bharti

Frances R. Wadelin

Paula M. Moran

Nigel P. Mongan

David M. Heery



Abstract

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.

Journal Article Type Article
Publication Date Nov 1, 2013
Journal Nucleic Acids Research
Print ISSN 0305-1048
Electronic ISSN 1362-4962
Publisher Oxford University Press (OUP)
Peer Reviewed Peer Reviewed
Volume 41
Issue 21
APA6 Citation Chan, C. M., Fulton, J., Montiel-Duarte, C., Collins, H. M., Bharti, N., Wadelin, F. R., …Heery, D. M. (2013). A signature motif mediating selective interactions of BCL11A with the NR2E/F subfamily of orphan nuclear receptors. Nucleic Acids Research, 41(21), doi:10.1093/nar/gkt761
DOI https://doi.org/10.1093/nar/gkt761
Publisher URL http://nar.oxfordjournals.org/content/41/21/9663
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
Additional Information This article has been accepted for publication in Nucleic Acids Research published by Oxford University Press.

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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