Promoter Activation by Enhancer-Dependent and -Independent Loading of Activator and Coactivator Complexes

Abstract

Activation of the pDbeta1 promoter at the TCRbeta locus requires a functional distal enhancer, Ebeta. Here, we have analyzed the mechanism of promoter activation in thymocytes from mice containing or lacking Ebeta. We found that pDbeta1 shows a complex profile of transcription factor and chromatin remodeling complex occupancy even at Ebeta(-) alleles. The presence of Ebeta, however, results in a few specific changes in factor occupancy at the promoter. These differences correlate with localized alterations in histone modifications and in the recruitment of the basal transcriptional machinery. In addition, Ebeta is also bound by CBP and Pol II, suggesting a mechanism for delivery of a holoenzyme complex to the pDbeta1 promoter. These results illustrate a specialized, long-range function of an enhancer in the hierarchical events that regulate assembly of a cell type-specific promoter.

The β-globinlocus control region (LCR) functions primarily by enhancing the transition from transcription initiation to elongation

“…Our results implicating a primary function of the LCR downstream of PIC assembly contrast with a recent report showing that the endogenous 3Ј TCR␤ enhancer (E␤) acts to modify chromatin and in the recruitment of pol II, TBP, and transactivators at the upstream pD␤1 promoter (Spicuglia et al 2002). Clearly, these differences could be due to different technical approaches (e.g., ChIP procedures).…”

The SWI/SNF complex and cancer

“…BRM and BRG1 play important roles in the immune system SWI/SNF plays an important role in immune responses, T-cell development and recombination events (Golding et al, 1999;Agalioti et al, 2000;Kwon et al, 2000;Spicuglia et al, 2002;Morshead et al, 2003). The SWI/ SNF complexes have been shown to remodel chromatin in such a way as to drive consecutive developmental transitions in T cells in response to external stimuli.…”

“…Variable-diversity-joining (V(D)J) recombination has also been shown to be mediated by SWI/SNF. BRG1 stimulates in vitro recombination of chromatin and is also bound to regions in the T-cell receptor (TCR) and immunoglobulin loci that take part in recombination events (Golding et al, 1999;Kwon et al, 2000;Spicuglia et al, 2002;Morshead et al, 2003;Patenge et al, 2004). More recent studies have shown SWI/SNF to be fundamental to the promoter-directed assembly of TCR-b (TCRB) genes (Osipovich et al, 2007); SWI/ SNF is recruited to promoters and then facilitates recombination by exposing segments of genomic DNA to V(D)J recombinase.…”

TCRβ Allelic Exclusion in Dynamical Models of V(D)J Recombination Based on Allele Independence

“…This being the case, the length of the window might have been overestimated. Alternatively, the values may cover additional events including the local epigenetic changes that in effect trigger this first rearrangement step (64,65); prompt Db-Jb transitions would have no biological reality (with little impact on our data because this option only bears on tiny cell percentages). In the future, thorough examination of Db-Jb recombination in DN cells, under single-cell assay conditions, may be necessary to close this debate.…”