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Thyroid hormone receptor, v-ErbA, and chromatin.

A P Wolffe¹, T N Collingwood, Q Li

¹Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-5431, USA.

Vitamins and Hormones

|February 11, 2000

Summary

Thyroid hormone receptor and v-erbA bind chromatin, altering its structure to regulate transcription. Ligand binding triggers a switch from corepressor to coactivator recruitment, demonstrating chromatin modification

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Area of Science:

Molecular Biology
Epigenetics
Gene Regulation

Background:

Thyroid hormone receptor (TR) and v-erbA are nuclear proteins stably associated with chromatin.
Unlike many regulators, TR binds both naked and nucleosomal DNA with similar affinity.

Purpose of the Study:

To investigate how chromatin structure facilitates TR and v-erbA association.
To understand the role of chromatin modification in TR-mediated transcription regulation.

Main Methods:

In vitro reconstitution experiments to study DNA-protein interactions.
In vivo genomic footprinting to analyze chromatin structure.
Assays to assess transcriptional repression and activation.

Main Results:

Related Experiment Videos

TR and v-erbA binding generates ligand-independent DNase I hypersensitive sites.
Unliganded TR/v-erbA associate with a corepressor complex (NCoR, SIN3, histone deacetylase) for transcriptional repression.
Ligand binding induces TR conformational change, releasing corepressors and recruiting coactivators (p300, PCAF) for chromatin remodeling and transcription activation.

Conclusions:

TR and v-erbA utilize stable chromatin association and modification for transcription regulation.
Targeted chromatin modification by TR provides a model for studying epigenetic regulation.