Liganded Thyroid Hormone Receptor Induces Nucleosome Removal and Histone Modifications to Activate Transcription during Larval Intestinal Cell Death and Adult Stem Cell Development

• Published in: Endocrinology (Philadelphia) Vol. 153; no. 2; pp. 961 - 972
• Main Authors: Matsuura, Kazuo, Fujimoto, Kenta, Fu, Liezhen, Shi, Yun-Bo
• Format: Journal Article
• Language: English
• Published: Chevy Chase, MD Oxford University Press 01.02.2012; Endocrine Society
• Subjects: Abnormalities; Animals; Antibodies; Antibody Specificity; Apoptosis; Biological and medical sciences; Cancer; Cell activation; Cell culture; Cell Death; Cell differentiation; Cell proliferation; Chromatin Assembly and Disassembly; Chromatin remodeling; Cofactors; Degeneration; Differentiation; DNA-directed RNA polymerase; DNA-Directed RNA Polymerases - metabolism; Energy metabolism; Epithelium; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Developmental - physiology; Gene regulation; Histones; Histones - metabolism; Intestine; Intestines - cytology; Larva - growth & development; Larva - metabolism; Ligands; Metabolism; Metamorphosis; Metamorphosis, Biological - physiology; Nucleosomes; Nucleosomes - metabolism; Promoter Regions, Genetic; Promoters; Receptors; Receptors, Thyroid Hormone - metabolism; RNA - genetics; RNA - metabolism; RNA polymerase; Stem Cells; Thyroid; Thyroid gland; Thyroid hormone receptors; Thyroid hormones; Thyroid-TRH-TSH; Transcription; Triiodothyronine; Triiodothyronine - metabolism; Vertebrates; Vertebrates: endocrinology; Xenopus; Transcription; Digestive system; Ligand; Cell death; Stem cell; Gut; Development; Thyroid hormone; Histone; Hormonal receptor
• ISSN: 0013-7227; 1945-7170; 1945-7170
• DOI: 10.1210/en.2011-1736

Thyroid hormone (T3) plays an important role in regulating multiple cellular and metabolic processes, including cell proliferation, cell death, and energy metabolism, in vertebrates. Dysregulation of T3 signaling results in developmental abnormalities, metabolic defects, and even cancer. We used T3-dependent Xenopus metamorphosis as a model to study how T3 regulates transcription during vertebrate development. T3 exerts its metamorphic effects through T3 receptors (TR). TR recruits, in a T3-dependent manner, cofactor complexes that can carry out chromatin remodeling/histone modifications. Whether and how histone modifications change upon gene regulation by TR during vertebrate development is largely unknown. Here we analyzed histone modifications at T3 target genes during intestinal metamorphosis, a process that involves essentially total apoptotic degeneration of the simple larval epithelium and de novo development of the adult epithelial stem cells, followed by their proliferation and differentiation into the complex adult epithelium. We demonstrated for the first time in vivo during vertebrate development that TR induces the removal of core histones at the promoter region and the recruitment of RNA polymerase. Furthermore, a number of histone activation and repression marks have been defined based on correlations with mRNA levels in cell cultures. Most but not all correlate with gene expression induced by liganded TR during development, suggesting that tissue and developmental context influences the roles of histone modifications in gene regulation. Our findings provide important mechanistic insights on how chromatin remodeling affects developmental gene regulation in vivo.