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Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators
Author(s) -
Huang Ningwu,
vom Baur Elmar,
Garnier JeanMarie,
Lerouge Thierry,
Vonesch JeanLuc,
Lutz Yves,
Chambon P.,
Losson Régine
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.12.3398
Subject(s) - nuclear receptor , biology , transcription factor , retinoid x receptor , corepressor , retinoic acid , retinoic acid receptor , microbiology and biotechnology , receptor , retinoid x receptor gamma , thyroid hormone receptor , biochemistry , gene
NSD1, a novel 2588 amino acid mouse nuclear protein that interacts directly with the ligand‐binding domain (LBD) of several nuclear receptors (NRs), has been identified and characterized. NSD1 contains a SET domain and multiple PHD fingers. In addition to these conserved domains found in both positive and negative Drosophila chromosomal regulators, NSD1 contains two distinct NR interaction domains, NID −L and NID +L , that exhibit binding properties of NIDs found in NR corepressors and coactivators, respectively. NID −L , but not NID +L , interacts with the unliganded LBDs of retinoic acid receptors (RAR) and thyroid hormone receptors (TR), and this interaction is severely impaired by mutations in the LBD α‐helix 1 that prevent binding of corepressors and transcriptional silencing by apo‐NRs. NID +L , but not NID −L , interacts with the liganded LBDs of RAR, TR, retinoid X receptor (RXR), and estrogen receptor (ER), and this interaction is abrogated by mutations in the LBD α‐helix 12 that prevent binding of coactivators of the ligand‐induced transcriptional activation function AF‐2. A novel variant (FxxLL) of the NR box motif (LxxLL) is present in NID +L and is required for the binding of NSD1 to holo‐LBDs. Interestingly, NSD1 contains separate repression and activation domains. Thus, NSD1 may define a novel class of bifunctional transcriptional intermediary factors playing distinct roles in both the presence and absence of ligand.