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This version published online on October 27, 2005
Molecular Endocrinology, doi:10.1210/me.2005-0101
A more recent version of this article appeared on March 1, 2006
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Submitted on February 24, 2005
Accepted on October 20, 2005

Thyroid hormone-regulated target genes have distinct patterns of co-activator recruitment and histone acetylation

Ying Liu, Xianmin Xia, Joseph D. Fondell, and Paul M. Yen*

Dept. Medicine, Johns Hopkins Bayview Medical Center, Johns Hopkins University, Baltimore, MD 21224; Mol. Regulation and Neuroendocrinology Section, Clinical Endocrinology Branch, NIDDK, Bethesda, MD 20892 ; Dept. of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854

* To whom correspondence should be addressed. E-mail: pyen3{at}jhmi.edu.

Thyroid hormone receptors (TRs) are ligand-regulated transcription factors that bind to thyroid hormone response elements of target genes. Upon ligand binding, they recruit co-activator complexes that increase histone acetylation and recruit RNA pol II to activate transcription. Recent studies suggest that nuclear receptors and co-activators 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 (ChIP) assays to investigate co-activator recruitment and histone acetylation patterns on the TREs of four endogenous target genes (GH, SERCA, PEPCK, and Cyp7) in a rat pituitary cell line that expresses TRs. We found that TR{beta}, several associated co-activators (SRC-1, GRIP-1, and TRAP220), and RNA Pol II were rapidly recruited to TREs 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 co-activators 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 co-activator recruitment and histone acetylation which may enable highly specific regulation.
Key words: co-activator • thyroid hormone receptor • transcription • chromatin immunoprecipitation assay

NURSA Molecule Pages Link:

Nuclear Receptors:   TRβ
Coregulators:   TRAP220  |  SRC-1  |  GRIP1
Ligands:   Thyroid hormone



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