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PMID: 12660164 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Thyroid hormone-regulated enhancer blocking: cooperation of CTCF and thyroid hormone receptor.

The EMBO journal ·Vol. 22 ·No. 7 ·2003-04-01 ·Pages 1579-87

Lutz M, Burke LJ, LeFevre P, Myers FA, Thorne AW, Crane-Robinson C, Bonifer C, Filippova GN, Lobanenkov V, Renkawitz R

Abstract

The highly conserved, ubiquitously expressed, zinc finger protein CTCF is involved in enhancer blocking, a mechanism crucial for shielding genes from illegitimate enhancer effects. Interestingly, CTCF-binding sites are often flanked by thyroid hormone response elements (TREs), as at the chicken lysozyme upstream silencer. Here we identify a similar composite site positioned upstream of the human c-myc gene. For both elements, we demonstrate that thyroid hormone abrogates enhancer blocking. Relief of enhancer blocking occurs even though CTCF remains bound to the lysozyme chromatin. Furthermore, chromatin immunoprecipitation analysis of the lysozyme upstream region revealed that histone H4 is acetylated at the CTCF-binding site. Loss of enhancer blocking by the addition of T3 led to increased histone acetylation, not only at the CTCF site, but also at the enhancer and the promoter. Thus, when TREs are adjacent to CTCF-binding sites, thyroid hormone can regulate enhancer blocking, thereby providing a new property for what was previously thought to be constitutive enhancer shielding by CTCF.

MeSH Terms
Acetylation Animals Base Sequence CCCTC-Binding Factor Chickens DNA-Binding Proteins/chemistry,genetics,physiology Electrophoretic Mobility Shift Assay Enhancer Elements, Genetic Histones/metabolism Humans K562 Cells Molecular Sequence Data Receptors, Thyroid Hormone/physiology Repressor Proteins Sequence Homology, Nucleic Acid Thyroid Hormones/physiology Transcription Factors/chemistry,genetics,physiology
Chemicals
CCCTC-Binding Factor CTCF protein, human DNA-Binding Proteins Histones Receptors, Thyroid Hormone Repressor Proteins Thyroid Hormones Transcription Factors
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Lutz Marcus
Institute for Genetics, Justus-Liebig-Universitaet Giessen, Heinrich-Buff-Ring 58-62, D-35392 Giessen, Germany.
Burke Les J
LeFevre Pascal
Myers Fiona A
Thorne Alan W
Crane-Robinson Colyn
Bonifer Constanze
Filippova Galina N
Lobanenkov Victor
Renkawitz Rainer
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg147
Published
2003-04-01
Pages
1579-87
Language
English
Region
England
NLM ID
8208664
PMCID
PMC152892
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdg147 PMC Full Text View journal details
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