The cellular retinoic acid binding protein I gene is induced by thyroid hormone (T3) through a T3 response element (TRE) approximately 1 kb upstream of the basal promoter. The upstream region is organized into a positioned nucleosomal array with the N1 nucleosome spanning the GC box region. T3 induces apparent interactions between chromatin segments containing the TRE and the GC box regions and the sliding of upstream nucleosomes toward N1 with concomitant N1 remodeling. Concurrently, the chromatin-remodeling factor BRM is replaced by BRG1 and histones are hyperacetylated. All these events are abolished in Med1/Trap220 null cells, indicating a key role for TRAP/Mediator in these processes. A MED1/TRAP220-containing Mediator complex constitutively occupies the GC box region but not the TRE, serving as a nexus for distal and proximal factors. This indicates new TRAP/Mediator functions in facilitating ultimate recruitment and function of RNA polymerase II and the general transcription machinery.
Bibliographical noteFunding Information:
This work was supported by NIH grants DK54733, DK60521, DA11190, and K02-DA13926 (to L.-N.W.) and NIH grant DK71900 (to R.G.R.). M.J.B. was supported by a Generalitat de Catalunya-Fulbright Postdoctoral Fellowship. We thank J. Bi, F.C. Walosin, S.D. Persaud, C.K. Hwang, and S.S. Kim for technical help.