A signature motif mediating selective interactions of BCL11A with the NR2E/F subfamily of orphan nuclear receptors

Chan, CM, Fulton, J, Montiel-Duarte, C ORCID: https://orcid.org/0000-0002-9144-8809, Collins, HM, Bharti, N, Wadelin, FR, Moran, PM, Mongan, NP and Heery, DM, 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

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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 twenty other LBDs 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.

Item Type:	Journal article
Publication Title:	Nucleic Acids Research
Creators:	Chan, C.M., Fulton, J., Montiel-Duarte, C., Collins, H.M., Bharti, N., Wadelin, F.R., Moran, P.M., Mongan, N.P. and Heery, D.M.
Publisher:	Oxford University Press
Date:	2013
Volume:	41
Number:	21
ISSN:	1362-4962
Identifiers:	Number Type 10.1093/nar/gkt761 DOI
Rights:	Copyright © 2013 Oxford University Press This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Nucleic Acids Research following peer review. The definitive publisher-authenticated version: CHAN, C.M., FULTON, J., MONTIEL-DUARTE, C., COLLINS, H.M., BHARTI, N., WADELIN, F.R., MORAN, P.M., MONGAN, N.P. and 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), pp. 9663-9679, is available online at: http://nar.oxfordjournals.org/content/41/21/9663.full.
Divisions:	Schools > School of Science and Technology
Record created by:	EPrints Services
Date Added:	09 Oct 2015 10:00
Last Modified:	09 Jun 2017 13:16
URI:	https://irep.ntu.ac.uk/id/eprint/6159

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