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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

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Control of nuclear receptor function by local chromatin structure.

Malgorzata Wiench¹, Tina B Miranda, Gordon L Hager

¹Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, Bethesda, MD 20892-5055, USA.

The FEBS Journal

|April 20, 2011

Summary

Steroid hormone receptors control gene expression tissue-specifically. Local chromatin structure, influenced by remodeling and modifying enzymes, dictates gene accessibility and cell-selective regulation.

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Area of Science:

Molecular Biology
Genetics
Epigenetics

Background:

Steroid hormone receptors (SHRs) mediate tissue-specific gene transcription.
Gene expression is tightly controlled by local chromatin structure at regulatory elements.

Purpose of the Study:

To elucidate the role of chromatin structure in regulating SHR-mediated gene transcription.
To understand how chromatin environments enable cell-selective gene regulation.

Main Methods:

Analysis of chromatin remodeling complexes.
Investigation of histone and DNA modifying enzymes.
Examination of transcription factor and co-regulator interactions.

Main Results:

Chromatin remodeling and modification enzymes create permissive or repressive chromatin environments.
Regulatory elements exhibit constitutive or receptor-dependent accessibility.
Chromatin states are established during development and differentiation.

Conclusions:

Local chromatin structure is a key determinant of tissue-specific SHR activity.
Cell-selective regulation of gene transcription is achieved through controlled access of regulatory factors to chromatin elements.