Transcriptional activation of NAD+-dependent protein deacetylase SIRT1 by nuclear receptor TLX.
An orphan nuclear receptor TLX is a transcriptional repressor that promotes the proliferation and self-renewal of neural precursor cells (NPCs). SIRT1, an NAD(+)-dependent protein deacetylase, is highly expressed in the NPCs and participates in neurogenesis. Here, we found that TLX colocalized with SIRT1 and knockdown of TLX by small interfering RNAs decreased SIRT1 levels in NPCs. TLX increased the SIRT1 expression by binding to the newly identified TLX-activating element in the SIRT1 gene promoter in HEK293 cells. Thus, TLX is an inducer of SIRT1 and may contribute to neurogenesis both as a transactivator and as a repressor.
Iwahara
Naotoshi
N
Department of Pharmacology, Sapporo Medical University, Sapporo 060-8556, Japan.
Hisahara
Shin
S
Hayashi
Takashi
T
Horio
Yoshiyuki
Y
D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D055495:Neurogenesis / Q000235:genetics; D057093:Orphan Nuclear Receptors; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics*; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation
C088601:NR2E1 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D015534:Trans-Activators; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins