Scacchetti Alessandro, Brueckner Laura, Jain Dhawal, Schauer Tamas, Zhang Xu, Schnorrer Frank, van Steensel Bas, Straub Tobias, Becker Peter B
Molecular Biology Division, Biomedical Center, Faculty of Medicine, Ludwig-Maximilian University Munich, Planegg-Martinsried, Germany.
Center for Integrated Protein Science Munich, München, Germany.
Life Sci Alliance. 2018 Feb 9;1(1):e201800024. doi: 10.26508/lsa.201800024. eCollection 2018 Jan.
The chromatin remodeling complexes chromatin accessibility complex and ATP-utilizing chromatin assembly and remodeling factor (ACF) combine the ATPase ISWI with the signature subunit ACF1. These enzymes catalyze well-studied nucleosome sliding reactions in vitro, but how their actions affect physiological gene expression remains unclear. Here, we explored the influence of chromatin accessibility complex/ACF on transcription by using complementary gain- and loss-of-function approaches. Targeting ACF1 to multiple reporter genes inserted at many different genomic locations revealed a context-dependent inactivation of poorly transcribed reporters in repressive chromatin. Accordingly, single-embryo transcriptome analysis of an knock-out allele showed that only lowly expressed genes are derepressed in the absence of ACF1. Finally, the nucleosome arrays in -deficient chromatin show loss of physiological regularity, particularly in transcriptionally inactive domains. Taken together, our results highlight that ACF1-containing remodeling factors contribute to the establishment of an inactive ground state of the genome through chromatin organization.
染色质重塑复合物染色质可及性复合物以及利用ATP的染色质组装与重塑因子（ACF）将ATP酶ISWI与标志性亚基ACF1结合在一起。这些酶在体外催化经过充分研究的核小体滑动反应，但其作用如何影响生理基因表达仍不清楚。在这里，我们通过使用互补的功能获得和功能丧失方法，探索了染色质可及性复合物/ACF对转录的影响。将ACF1靶向插入许多不同基因组位置的多个报告基因，揭示了在抑制性染色质中低转录报告基因的背景依赖性失活。因此，对一个敲除等位基因的单胚胎转录组分析表明，在没有ACF1的情况下，只有低表达基因的抑制被解除。最后，ACF1缺陷染色质中的核小体阵列显示出生理规律性的丧失，特别是在转录非活性结构域。综上所述，我们的结果突出表明，含ACF1的重塑因子通过染色质组织有助于建立基因组的非活性基态。
