The Interaction of NF-κB Transcription Factor with Centromeric Chromatin

NF-κB转录因子与着丝粒染色质的相互作用

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Abstract

Centromeric chromatin is a subset of chromatin structure and governs chromosome segregation. The centromere is composed of both CENP-A nucleosomes (CENP-A(nuc)) and H3 nucleosomes (H3(nuc)) and is enriched with alpha-satellite (α-sat) DNA repeats. These CENP-A(nuc) have a different structure than H3(nuc), decreasing the base pairs (bp) of wrapped DNA from 147 bp for H3(nuc) to 121 bp for CENP-A(nuc). All these factors can contribute to centromere function. We investigated the interaction of H3(nuc) and CENP-A(nuc) with NF-κB, a crucial transcription factor in regulating immune response and inflammation. We utilized atomic force microscopy (AFM) to characterize complexes of both types of nucleosomes with NF-κB. We found that NF-κB unravels H3(nuc), removing more than 20 bp of DNA, and that NF-κB binds to the nucleosomal core. Similar results were obtained for the truncated variant of NF-κB comprised only of the Rel homology domain and missing the transcription activation domain (TAD), suggesting that RelA(TAD) is not critical in unraveling H3(nuc). By contrast, NF-κB did not bind to or unravel CENP-A(nuc). These findings with different affinities for two types of nucleosomes to NF-κB may have implications for understanding the mechanisms of gene expression in bulk and centromere chromatin.

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