Mueller Britta, Mieczkowski Jakub, Kundu Sharmistha, Wang Peggy, Sadreyev Ruslan, Tolstorukov Michael Y, Kingston Robert E
Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Genes Dev. 2017 Mar 1;31(5):451-462. doi: 10.1101/gad.293118.116. Epub 2017 Mar 29.
Activation of transcription requires alteration of chromatin by complexes that increase the accessibility of nucleosomal DNA. Removing nucleosomes from regulatory sequences has been proposed to play a significant role in activation. We tested whether changes in nucleosome occupancy occurred on the set of genes that is activated by the unfolded protein response (UPR). We observed no decrease in occupancy on most promoters, gene bodies, and enhancers. Instead, there was an increase in the accessibility of nucleosomes, as measured by micrococcal nuclease (MNase) digestion and ATAC-seq (assay for transposase-accessible chromatin [ATAC] using sequencing), that did not result from removal of the nucleosome. Thus, changes in nucleosome accessibility predominate over changes in nucleosome occupancy during rapid transcriptional induction during the UPR.
转录激活需要复合物改变染色质结构,以增加核小体DNA的可及性。有观点认为,从调控序列上去除核小体在激活过程中发挥着重要作用。我们测试了在由未折叠蛋白反应(UPR)激活的基因集上,核小体占据情况是否发生了变化。我们观察到,大多数启动子、基因体和增强子上的核小体占据并没有减少。相反,通过微球菌核酸酶(MNase)消化和ATAC-seq(利用测序技术检测转座酶可及染色质[ATAC])测量发现,核小体的可及性增加了,而这并非是由于核小体的去除所致。因此,在UPR快速转录诱导过程中,核小体可及性的变化比核小体占据情况的变化更为显著。