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Molecular and genetic studies of histone‐modifying complexes in thyroid hormone action during Xenopus development.
Author(s) -
Shi YunBo
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.456.11
Subject(s) - metamorphosis , biology , corepressor , psychological repression , histone deacetylase , thyroid hormone receptor , gene , histone , coactivator , genetics , microbiology and biotechnology , gene expression , transcription factor , botany , larva
Thyroid hormone (T3) plays a causative role in frog metamorphosis. T3 functions to alter gene expression through T3 receptor (TR). We have analyzed the role of TR‐binding cofactor complexes during frog development. We will show that the histone acetylase/methylase‐containing coactivator complexes SCR/p300//PRMT1 are recruited by liganded TR to endogenous target genes. More importantly, these complexes are necessary for gene regulation by TR and frog metamorphosis and their levels regulate the rate of metamorphosis. On the other hand, during premetamorphic development, unliganded TR recruits histone deacetylase complexes containing TR‐binding corepressors N‐CoR/SMRT. Disrupting the recruitment of corepressor complexes with a dominant negative form of N‐CoR leads to derepression of T3‐response genes in transgenic animals. Interestingly, transgenic tadpoles develop faster than wild type siblings, initiating metamorphosis by as much as 7 days earlier out of the 30‐day experiment. These data thus demonstrate that deacetylase complexes participate in gene repression to control metamorphic timing while acetylase/methylase complexes are involved in gene activation to control the rate of metamorphosis. The similarities between metamorphosis and postembryonic development in mammals suggest that such mechanisms are conserved during evolution.