title: Thyroid hormone-regulated target genes have distinct patterns of coactivator recruitment and histone acetylation.
abstract: Thyroid hormone receptors (TRs) are ligand-regulated transcription factors that bind to thyroid hormone response elements of target genes. Upon ligand binding, they recruit coactivator complexes that increase histone acetylation and recruit RNA polymerase II (Pol II) to activate transcription. Recent studies suggest that nuclear receptors and coactivators may have temporal recruitment patterns on hormone response elements, yet little is known about the nature of the patterns at multiple endogenous target genes. We thus performed chromatin immunoprecipitation assays to investigate coactivator recruitment and histone acetylation patterns on the thyroid hormone response elements of four endogenous target genes (GH, sarcoplasmic endoplasmic reticulum calcium-adenosine triphosphatase, phosphoenolpyruvate carboxykinase, and cholesterol 7alpha-hydroxylase) in a rat pituitary cell line that expresses TRs. We found that TRbeta, several associated coactivators (steroid receptor coactivator-1, glucocorticoid receptor interacting protein-1, and TR-associated protein 220), and RNA Pol II were rapidly recruited to thyroid hormone response elements as early as 15 min after T3 addition. When the four target genes were compared, we observed differences in the types and temporal patterns of recruited coactivators and histone acetylation. Interestingly, the temporal pattern of RNA Pol II was similar for three genes studied. Our findings suggest that thyroid hormone-regulated target genes may have distinct patterns of coactivator recruitment and histone acetylation that may enable highly specific regulation.
authors.affiliation: Endocrinology Division, Department of Medicine, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, Room B114, Baltimore, Maryland 21224, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Xianmin
authors.initials: X
authors.lastname: Xia
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Fondell
authors.forename: Paul M
authors.initials: PM
authors.lastname: Yen
mesh_terms: D000107:Acetylation; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism*; D056913:Mediator Complex Subunit 1; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020218:Response Elements; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D037042:Thyroid Hormone Receptors beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D006657:Histones; C538857:Med1 protein, rat; D056913:Mediator Complex Subunit 1; D051958:Nuclear Receptor Coactivator 2; D037042:Thyroid Hormone Receptors beta; D015534:Trans-Activators; D014157:Transcription Factors; D014284:Triiodothyronine; D013006:Growth Hormone; D002790:Cholesterol 7-alpha-Hydroxylase; D051548:Histone Acetyltransferases; D056920:Nuclear Receptor Coactivator 1; D012319:RNA Polymerase II; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D000252:Calcium-Transporting ATPases