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Sökning: id:"swepub:oai:lup.lub.lu.se:c7e00628-3000-42d3-8057-c17f4ed1f86a" > Myt1l safeguards ne...

  • Mall, MoritzStanford University (författare)

Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates

  • Artikel/kapitelEngelska2017

Förlag, utgivningsår, omfång ...

  • 2017-04-05
  • Springer Science and Business Media LLC,2017

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:c7e00628-3000-42d3-8057-c17f4ed1f86a
  • https://lup.lub.lu.se/record/c7e00628-3000-42d3-8057-c17f4ed1f86aURI
  • https://doi.org/10.1038/nature21722DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:135588363URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • Normal differentiation and induced reprogramming require the activation of target cell programs and silencing of donor cell programs. In reprogramming, the same factors are often used to reprogram many different donor cell types. As most developmental repressors, such as RE1-silencing transcription factor (REST) and Groucho (also known as TLE), are considered lineage-specific repressors, it remains unclear how identical combinations of transcription factors can silence so many different donor programs. Distinct lineage repressors would have to be induced in different donor cell types. Here, by studying the reprogramming of mouse fibroblasts to neurons, we found that the pan neuron-specific transcription factor Myt1-like (Myt1l) exerts its pro-neuronal function by direct repression of many different somatic lineage programs except the neuronal program. The repressive function of Myt1l is mediated via recruitment of a complex containing Sin3b by binding to a previously uncharacterized N-terminal domain. In agreement with its repressive function, the genomic binding sites of Myt1l are similar in neurons and fibroblasts and are preferentially in an open chromatin configuration. The Notch signalling pathway is repressed by Myt1l through silencing of several members, including Hes1. Acute knockdown of Myt1l in the developing mouse brain mimicked a Notch gain-of-function phenotype, suggesting that Myt1l allows newborn neurons to escape Notch activation during normal development. Depletion of Myt1l in primary postmitotic neurons de-repressed non-neuronal programs and impaired neuronal gene expression and function, indicating that many somatic lineage programs are actively and persistently repressed by Myt1l to maintain neuronal identity. It is now tempting to speculate that similar 'many-but-one' lineage repressors exist for other cell fates; such repressors, in combination with lineage-specific activators, would be prime candidates for use in reprogramming additional cell types.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Kareta, Michael S.Stanford University,Sanford Research (författare)
  • Chanda, SohamStanford University (författare)
  • Ahlenius, HenrikLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Stamceller, åldrande och neurodegeneration,Forskargrupper vid Lunds universitet,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Stem Cells, Aging and Neurodegeneration,Lund University Research Groups(Swepub:lu)neur-hah (författare)
  • Perotti, NicholasStanford University (författare)
  • Zhou, BoStanford University (författare)
  • Grieder, Sarah D.Stanford University (författare)
  • Ge, XuecaiStanford University,University of California, Merced (författare)
  • Drake, SiennaLund University (författare)
  • Euong Ang, CheenStanford University (författare)
  • Walker, Brandon M.Stanford University (författare)
  • Vierbuchen, ThomasHarvard Medical School,Stanford University (författare)
  • Fuentes, Daniel R.Stanford University (författare)
  • Brennecke, PhilipLeibniz-Institute for Molecular Pharmacology (FMP),Stanford University (författare)
  • Nitta, Kazuhiro R.Karolinska Institute,RIKEN Nishina Center for Accelerator-Based Science (författare)
  • Jolma, ArttuKarolinska Institutet,Karolinska Institute (författare)
  • Steinmetz, Lars M.European Molecular Biology Laboratory Heidelberg,Stanford University (författare)
  • Taipale, JussiKarolinska Institutet,Karolinska Institute,University of Helsinki (författare)
  • Südhof, Thomas C.Stanford University (författare)
  • Wernig, MariusStanford University (författare)
  • Stanford UniversitySanford Research (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Nature: Springer Science and Business Media LLC544:7649, s. 245-2490028-08361476-4687

Internetlänk

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  • Nature (Sök värdpublikationen i LIBRIS)

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