4.8 Article

Nipbl Interacts with Zfp609 and the Integrator Complex to Regulate Cortical Neuron Migration

期刊

NEURON
卷 93, 期 2, 页码 348-361

出版社

CELL PRESS
DOI: 10.1016/j.neuron.2016.11.047

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资金

  1. FEBS Long-Term Fellowship
  2. Netherlands Organization for Scientific Research (NWO)
  3. National Roadmap Large-Scale Research Facilities of the Netherlands [184.032.201]
  4. Francis Crick Institute
  5. Cancer Research UK [FC0010089]
  6. UK Medical Research Council [FC0010089]
  7. Wellcome Trust [FC0010089, 106187/Z/14/Z]
  8. UK Biotechnology and Biological Sciences Research Council [BB/K005316/1, U117570528]
  9. Wellcome Trust [106187/Z/14/Z] Funding Source: Wellcome Trust
  10. Biotechnology and Biological Sciences Research Council [BB/K005316/1] Funding Source: researchfish
  11. Medical Research Council [MR/M023907/1] Funding Source: researchfish
  12. The Francis Crick Institute [10309, 10089] Funding Source: researchfish
  13. Wellcome Trust [106187/Z/14/Z] Funding Source: researchfish
  14. BBSRC [BB/K005316/1] Funding Source: UKRI
  15. MRC [MR/M023907/1] Funding Source: UKRI

向作者/读者索取更多资源

Mutations in NIPBL are the most frequent cause of Cornelia de Lange syndrome (CdLS), a developmental disorder encompassing several neurological defects, including intellectual disability and seizures. How NIPBL mutations affect brain development is not understood. Here we identify Nipbl as a functional interaction partner of the neural transcription factor Zfp609 in brain development. Depletion of Zfp609 or Nipbl from cortical neural progenitors in vivo is detrimental to neuronal migration. Zfp609 and Nipbl overlap at genomic binding sites independently of cohesin and regulate genes that control cortical neuron migration. We find that Zfp609 and Nipbl interact with the Integrator complex, which functions in RNA polymerase 2 pause release. Indeed, Zfp609 and Nipbl co-localize at gene promoters containing paused RNA polymerase 2, and Integrator similarly regulates neuronal migration. Our data provide a rationale and mechanistic insights for the role of Nipbl in the neurological defects associated with CdLS.

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