Thyroid hormone-regulated enhancer blocking: cooperation of CTCF and thyroid hormone receptor.
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.
Lutz
Marcus
M
Institute for Genetics, Justus-Liebig-Universitaet Giessen, Heinrich-Buff-Ring 58-62, D-35392 Giessen, Germany.
Burke
Les J
LJ
LeFevre
Pascal
P
Myers
Fiona A
FA
Thorne
Alan W
AW
Crane-Robinson
Colyn
C
Bonifer
Constanze
C
Filippova
Galina N
GN
Lobanenkov
Victor
V
Renkawitz
Rainer
R
D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D000076246:CCCTC-Binding Factor; D002645:Chickens; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic; D006657:Histones / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D008969:Molecular Sequence Data; D011988:Receptors, Thyroid Hormone / Q000502:physiology*; D012097:Repressor Proteins; D012689:Sequence Homology, Nucleic Acid; D013963:Thyroid Hormones / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D004268:DNA-Binding Proteins; D006657:Histones; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; D013963:Thyroid Hormones; D014157:Transcription Factors