Wiechens Nicola, Singh Vijender, Gkikopoulos Triantaffyllos, Schofield Pieta, Rocha Sonia, Owen-Hughes Tom
Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
PLoS Genet. 2016 Mar 28;12(3):e1005940. doi: 10.1371/journal.pgen.1005940. eCollection 2016 Mar.
Within the genomes of metazoans, nucleosomes are highly organised adjacent to the binding sites for a subset of transcription factors. Here we have sought to investigate which chromatin remodelling enzymes are responsible for this. We find that the ATP-dependent chromatin remodelling enzyme SNF2H plays a major role organising arrays of nucleosomes adjacent to the binding sites for the architectural transcription factor CTCF sites and acts to promote CTCF binding. At many other factor binding sites SNF2H and the related enzyme SNF2L contribute to nucleosome organisation. The action of SNF2H at CTCF sites is functionally important as depletion of CTCF or SNF2H affects transcription of a common group of genes. This suggests that chromatin remodelling ATPase's most closely related to the Drosophila ISWI protein contribute to the function of many human gene regulatory elements.
在后生动物的基因组中,核小体在一类转录因子的结合位点附近高度有序排列。在此,我们试图研究是哪些染色质重塑酶负责这一过程。我们发现,依赖ATP的染色质重塑酶SNF2H在组织与结构转录因子CTCF位点的结合位点相邻的核小体阵列中起主要作用,并促进CTCF的结合。在许多其他因子结合位点,SNF2H和相关酶SNF2L也参与核小体的组织。SNF2H在CTCF位点的作用在功能上很重要,因为CTCF或SNF2H的缺失会影响一组共同基因的转录。这表明,与果蝇ISWI蛋白关系最密切的染色质重塑ATP酶对许多人类基因调控元件的功能有贡献。