Remodeling of perturbed chromatin can initiate de novo transcriptional and post- transcriptional silencing

• 成果类型: Article
• 署名作者: Carlier, Florian; Ramirez, Sebastian Castro; Kilani, Jaafar; Chehboub, Sara; Loiodice, Isabelle; Taddei, Angela; Gladyshev, Eugene
• 署名单位: Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Sorbonne Universite; UNICANCER; Universite PSL; Institut Curie; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13450
• DOI: 10.1073/pnas.2402944121
• 发表日期: 2024-07-30
• 关键词: dependent rna-polymerase; neurospora-crassa; homologous recombination; heterochromatin formation; dna methylation; factor atrx; r-loops; gene; sequence; mechanism

摘要

In eukaryotes, repetitive DNA can become silenced de novo, either transcriptionally or post- transcriptionally, by processes independent of strong sequence- specific cues. The mechanistic nature of such processes remains poorly understood. We found that in the fungus Neurospora crassa, de novo initiation of both transcriptional and post- transcriptional silencing was linked to perturbed chromatin, which was produced experimentally by the aberrant activity of transcription factors at the tetO operator array. Transcriptional silencing was mediated by canonical constitutive heterochromatin. On the other hand, post- transcriptional silencing resembled repeat- induced quelling but occurred normally when homologous recombination was inactivated. All silencing of the tetO array was dependent on SAD- 6, fungal ortholog of the SWI/ SNF chromatin remodeler ATRX (Alpha Thalassemia/Mental Retardation Syndrome X- Linked), which was required to maintain nucleosome occupancy at the perturbed locus. In addition, we found that two other types of sequences (the lacO array and native AT- rich DNA) could also undergo recombination- independent quelling associated with perturbed chromatin. These results suggested a model in which the de novo initiation of transcriptional and post- transcriptional silencing is coupled to the remodeling of perturbed chromatin.