title: Liganded thyroid hormone receptor induces nucleosome removal and histone modifications to activate transcription during larval intestinal cell death and adult stem cell development.
abstract: Thyroid hormone (T(3)) plays an important role in regulating multiple cellular and metabolic processes, including cell proliferation, cell death, and energy metabolism, in vertebrates. Dysregulation of T(3) signaling results in developmental abnormalities, metabolic defects, and even cancer. We used T(3)-dependent Xenopus metamorphosis as a model to study how T(3) regulates transcription during vertebrate development. T(3) exerts its metamorphic effects through T(3) receptors (TR). TR recruits, in a T(3)-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 T(3) 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.
authors.affiliation: National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Laboratory of Gene Regulation and Development, Bethesda, Maryland 20892, USA.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Matsuura
authors.forename: Kenta
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Liezhen
authors.initials: L
authors.lastname: Fu
authors.forename: Yun-Bo
authors.initials: YB
authors.lastname: Shi
mesh_terms: D000818:Animals; D000906:Antibodies; D000918:Antibody Specificity; D016923:Cell Death; D042002:Chromatin Assembly and Disassembly; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D007422:Intestines / Q000166:cytology*; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D008024:Ligands; D008675:Metamorphosis, Biological / Q000502:physiology; D009707:Nucleosomes / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D013234:Stem Cells; D014284:Triiodothyronine / Q000378:metabolism*; D014981:Xenopus
chemical_list: D000906:Antibodies; D006657:Histones; D008024:Ligands; D009707:Nucleosomes; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D012313:RNA; D012321:DNA-Directed RNA Polymerases