Loading…
Separate necdin domains bind ARNT2 and HIF1α and repress transcription
PWS is caused by the loss of expression of a set of maternally imprinted genes including NECDIN (NDN). NDN is expressed in post-mitotic neurons and plays an essential role in PWS as mouse models lacking only the Ndn gene mimic aspects of this disease. Patients haploid for SIM1 develop a PW-like synd...
Saved in:
Published in: | Biochemical and biophysical research communications 2007-11, Vol.363 (1), p.113-118 |
---|---|
Main Authors: | , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | PWS is caused by the loss of expression of a set of maternally imprinted genes including
NECDIN (NDN).
NDN is expressed in post-mitotic neurons and plays an essential role in PWS as mouse models lacking only the
Ndn gene mimic aspects of this disease. Patients haploid for
SIM1 develop a PW-like syndrome. Here, we report that NDN directly interacts with ARNT2, a bHLH-PAS protein and dimer partner for SIM1. We also found that NDN can interact with HIF1α. We showed that NDN can repress transcriptional activation mediated by ARNT2:SIM1 as well as ARNT2:HIF1α. The N-terminal 115 residues of NDN are sufficient for interaction with the bHLH domains of ARNT2 or HIF1α but not for transcriptional repression. Using GAL4-NDN fusion proteins, we determined that NDN possesses multiple repression domains. We thus propose that NDN regulates neuronal function and hypoxic response by regulating the activities of the ARNT2:SIM1 and ARNT2:HIF1α dimers, respectively. |
---|---|
ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1016/j.bbrc.2007.08.108 |