Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2013

Genome-wide analysis of thyroid hormone receptors shared and specific functions in neural cells

Rôle de l’hormone thyroïdienne T3 dans la régénération axonale chez les vertébrés supérieurs

Hasan Avci
  • Function : Author
Clement Lebrun
  • Function : Author
Rosine Wehrle
  • Function : Author
Mohamed Doulazmi
Marie-Pierre Morel
  • Function : Author
Masatsugu Ema
  • Function : Author
Guilan Vodjdani
  • Function : Author
Constantino Sotelo
  • Function : Author
Isabelle Dusart
Fabrice Chatonnet
  • Function : Author
Romain Guyot
  • Function : Author
Gérard Benoit
  • Function : Author

Abstract

TRα1 and TRβ1, the two main thyroid hormone receptors in mammals, are transcription factors that share similar properties. However, their respective functions are very different. This functional divergence might be explained in two ways: it can reflect different expression patterns or result from different intrinsic properties of the receptors. We tested this second hypothesis by comparing the repertoires of 3,3',5-triiodo-L-thyronine (T3)-responsive genes of two neural cell lines, expressing either TRα1 or TRβ1. Using transcriptome analysis, we found that a substantial fraction of the T3 target genes display a marked preference for one of the two receptors. So when placed alone in identical situations, the two receptors have different repertoires of target genes. Chromatin occupancy analysis, performed at a genome-wide scale, revealed that TRα1 and TRβ1 cistromes were also different. However, receptor-selective regulation of T3 target genes did not result from receptor-selective chromatin occupancy of their promoter regions. We conclude that modification of TRα1 and TRβ1 intrinsic properties contributes in a large part to the divergent evolution of the receptors' function, at least during neurodevelopment.

Dates and versions

hal-03278425 , version 1 (05-07-2021)

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Hasan Avci, Clement Lebrun, Rosine Wehrle, Mohamed Doulazmi, Marie-Pierre Morel, et al.. Genome-wide analysis of thyroid hormone receptors shared and specific functions in neural cells. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110 (8), pp.E766-E775. ⟨10.1073/pnas.1210626110⟩. ⟨hal-03278425⟩
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