The Chromatin Remodelling Enzymes SNF2H and SNF2L Position Nucleosomes adjacent to CTCF and Other Transcription Factors

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（metazoans）的基因组中，核小体（nucleosomes）在部分转录因子结合位点的邻近区域呈现高度有序的排布。本研究旨在探究介导这一有序排布的染色质重塑酶（chromatin remodelling enzyme）。我们发现，依赖ATP的染色质重塑酶（ATP-dependent chromatin remodelling enzyme）SNF2H在与架构性转录因子（architectural transcription factor）CTCF结合位点相邻的核小体阵列的有序排布中发挥核心作用，并可促进CTCF的结合。在诸多其他因子结合位点处，SNF2H与其同源酶SNF2L共同参与核小体的有序排布。SNF2H在CTCF结合位点的调控作用具有功能重要性：敲低CTCF或SNF2H均可影响同一组基因的转录水平。上述结果表明，与果蝇（Drosophila）ISWI蛋白（ISWI protein）亲缘关系最近的染色质重塑ATP酶（chromatin remodelling ATPase），参与了诸多人类基因调控元件（gene regulatory elements）的功能发挥。