Both CTCF-dependent and -independent insulators are found between the mouse T cell receptor alpha and Dad1 genes.
The T cell rearrangement of the T cell receptor (TCR) genes TCRalpha and delta is specifically regulated by a complex interplay between enhancer elements and chromatin structure. The alpha enhancer is active in T cells and drives TCRalpha recombination in collaboration with a locus control region-like element located downstream of the Calpha gene on mouse chromosome 14. Twelve kb further down-stream lies another gene, Dad1, with a program of expression different from that of TCRalpha. The approximately 6-kb locus control region element lying between them contains multiple regulatory sites with a variety of roles in regulating the two genes. Previous evidence has indicated that among these there are widely distributed regions with enhancer blocking (insulating) activity. We have shown in this report that one of these sites, not previously examined, strongly binds the insulator protein CCTC-binding factor (CTCF) in vitro and in vivo and can function in an enhancer blocking assay. However, other regions within the 6-kb element that also can block enhancers clearly do not harbor CTCF sites and thus must reflect the presence of a previously undetected and distinct vertebrate insulator activity.
Magdinier
Frédérique
F
Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0504, USA.
Yusufzai
Timur M
TM
Felsenfeld
Gary
G
D000107:Acetylation; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D019673:Genes, T-Cell Receptor alpha; D006657:Histones / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D015530:Nuclear Matrix / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; C489987:Dad1 protein, mouse; D006657:Histones; D008565:Membrane Proteins; D012097:Repressor Proteins