TY - JOUR
T1 - Identification of a novel modulator of thyroid hormone receptor-mediated action
AU - Baumgartner, Bernhard G.
AU - Orpinell, Meritxell
AU - Duran, Jordi
AU - Ribas, Vicent
AU - Burghardt, Hans E.
AU - Bach, Daniel
AU - Villar, Ana Victoria
AU - Paz, José C.
AU - González, Meritxell
AU - Camps, Marta
AU - Oriola, Josep
AU - Rivera, Francisca
AU - Palacín, Manuel
AU - Zorzano, Antonio
PY - 2007/11/21
Y1 - 2007/11/21
N2 - Background. Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle. Methodology/Principal Findings. We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from ohese diabetic rats. DOR expression is up-regulated during muscle differentiation and its loss-of-function has a negative impact on gene expression programmes linked to myogenesis or driven by thyroid hormones. In agreement with this, DOR enhances the transcriptional activity of the thyroid hormone receptor TRα1. This function is driven by the N-terminal part of the protein. Moreover, DOR physically interacts with TRα1 and to TRα1-responsive promoters, as shown by ChIP assays. T3 stimulation also promotes the mobilization of DOR from its localization in nuclear PML bodies, thereby indicating that its nuclear localization and cellular function may be related. Conclusions/Signifance. Our data indicate that DOR modulates thyroid hormone function and controls myogenesis. DOR expression is down-regulated in skeletal muscle in diabetes, This finding may be of relevance for thp alterations in muscle function associated with this disease.
AB - Background. Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle. Methodology/Principal Findings. We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from ohese diabetic rats. DOR expression is up-regulated during muscle differentiation and its loss-of-function has a negative impact on gene expression programmes linked to myogenesis or driven by thyroid hormones. In agreement with this, DOR enhances the transcriptional activity of the thyroid hormone receptor TRα1. This function is driven by the N-terminal part of the protein. Moreover, DOR physically interacts with TRα1 and to TRα1-responsive promoters, as shown by ChIP assays. T3 stimulation also promotes the mobilization of DOR from its localization in nuclear PML bodies, thereby indicating that its nuclear localization and cellular function may be related. Conclusions/Signifance. Our data indicate that DOR modulates thyroid hormone function and controls myogenesis. DOR expression is down-regulated in skeletal muscle in diabetes, This finding may be of relevance for thp alterations in muscle function associated with this disease.
UR - http://www.scopus.com/inward/record.url?scp=43149102536&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0001183
DO - 10.1371/journal.pone.0001183
M3 - Article
C2 - 18030323
AN - SCOPUS:43149102536
SN - 1932-6203
VL - 2
JO - PLoS ONE
JF - PLoS ONE
IS - 11
M1 - e1183
ER -
