Reader Comments
Post a new comment on this article
Post Your Discussion Comment
Please follow our guidelines for comments and review our competing interests policy. Comments that do not conform to our guidelines will be promptly removed and the user account disabled. The following must be avoided:
- Remarks that could be interpreted as allegations of misconduct
- Unsupported assertions or statements
- Inflammatory or insulting language
Thank You!
Thank you for taking the time to flag this posting; we review flagged postings on a regular basis.
closeIncorrect reference and fact
Posted by till on 25 Jan 2011 at 10:56 GMT
Typically upon ligand binding, PPAR-γ heterodimerizes with Retinoid Acid Receptor (RXR) and binds to PPAR-Response-Elements (PPRE) on target genes resulting in a transcriptional response [29]
http://plosone.org/article/info:doi/10.1371/journal.pone.0015909#article1.body1.sec1.p3
In the review cited, it is not stated that PPARg binds DNA upon ligand binding. Furthermore, DNA binding of PPARs is constitutive, as extensively shown by genome-wide interaction studies (e.g., "PPARg and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale", Lefterova et al., Genes Dev 22:2941–2952, 2008, and others).
RE: Incorrect reference and fact
till replied to till on 25 Jan 2011 at 14:14 GMT
The citation I am referring to is no. 29 (Tontonoz & Spiegelman). The sentence is "Typically upon ligand binding, PPAR-γ heterodimerizes with Retinoid Acid Receptor (RXR) and binds to PPAR-Response-Elements (PPRE) on target genes resulting in a transcriptional response [29]."
RE: Incorrect reference and fact
tthatcher replied to till on 08 Feb 2013 at 04:50 GMT
Thank you for your comment. We may not have picked the best reference for that point. However, there are numerous papers that discuss ligand-dependent binding of PPARgamma and RXR to DNA, going back to Issemann (1993).
The Lefterova genome wide study you site was performed with NIH-3T3L1 cells grown in media containing 10% FBS. FBS contains numerous fatty acids, many of which are ligands for PPARgamma, so it is not surprising to find a substantial background level of PPARgamma DNA binding in the absence of stimulation with additional exogenous PPARgamma ligands. It is possible that under physiological conditions, there are sufficient fatty acids present that PPARgamma is constitutively active at a low level (detectable by very sensitive PCR-based methods), but I do not think there is enough evidence to say that it is constitutively active without ligand. And there is certainly much evidence that exogenous ligands can up-regulate PPARgamma activity.