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

Ying Liu1, Xianmin Xia, Joseph D Fondell

  • 1Endocrinology Division, Department of Medicine, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, Room B114, Baltimore, Maryland 21224, USA.

Molecular Endocrinology (Baltimore, Md.)
|October 29, 2005
PubMed

Insights

Thyroid hormone receptors (TRs) rapidly recruit coactivators and RNA polymerase II to target genes. Distinct temporal patterns of coactivator recruitment and histone acetylation suggest specific gene regulation by thyroid hormone.

Area of Science:

  • Molecular Endocrinology
  • Gene Regulation
  • Chromatin Biology

Background:

  • Thyroid hormone receptors (TRs) are transcription factors activated by thyroid hormone.
  • TRs recruit coactivators to increase histone acetylation and activate gene transcription.
  • The temporal dynamics of coactivator recruitment at endogenous TR target genes are not well understood.

Purpose of the Study:

  • To investigate the temporal patterns of coactivator recruitment and histone acetylation at four endogenous TR target genes.
  • To determine if these patterns differ across target genes.

Main Methods:

  • Chromatin immunoprecipitation (ChIP) assays were performed in a rat pituitary cell line.
  • Coactivator recruitment and histone acetylation were analyzed at the thyroid hormone response elements (TREs) of four target genes (GH, SERCA, PEPCK, CH)।
  • Analysis was conducted at various time points after addition of thyroid hormone (T3).

Main Results:

  • TRbeta, coactivators (SRC-1, GRIP-1, TRAP220), and RNA polymerase II (Pol II) were rapidly recruited to TREs within 15 minutes of T3 addition.
  • Significant differences were observed in the types and temporal patterns of coactivator recruitment and histone acetylation across the four target genes.
  • The temporal recruitment pattern of Pol II was similar for three of the four target genes studied.

Conclusions:

  • Thyroid hormone-regulated target genes exhibit distinct patterns of coactivator recruitment and histone acetylation.
  • These distinct patterns suggest a mechanism for highly specific gene regulation by thyroid hormone.
  • The conserved temporal recruitment of Pol II implies a common downstream transcriptional initiation step.

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