Both CTCF-dependent and -independent Insulators Are Found between the Mouse T Cell Receptor α and Dad1 Genes

Frédérique Magdinier (1) , Timur M. Yusufzai (1) , Gary Felsenfeld (1)

1 NIDDK - Laboratory of Biological Modeling

The T cell rearrangement of the T cell receptor (TCR) genes TCRα and δ is specifically regulated by a complex interplay between enhancer elements and chromatin structure. The α enhancer is active in T cells and drives TCRα recombination in collaboration with a locus control region-like element located downstream of the Cα gene on mouse chromosome 14. Twelve kb further down-stream lies another gene, Dad1, with a program of expression different from that of TCRα. The ∼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.

Domaines: Immunologie; Biochimie, Biologie Moléculaire

Frédérique Magdinier, Timur M. Yusufzai, Gary Felsenfeld. Both CTCF-dependent and -independent Insulators Are Found between the Mouse T Cell Receptor α and Dad1 Genes. Journal of Biological Chemistry, 2004, 279 (24), pp.25381-25389. ⟨10.1074/jbc.M403121200⟩. ⟨hal-01663904⟩