The histone chaperone CAF-1 safeguards somatic cell identity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Sihem Cheloufi, Ulrich Elling, Barbara Hopfgartner, Youngsook L. Jung, Jernej Murn, Maria Ninova, Maria Hubmann, Aimee I. Badeaux, Cheen Euong Ang, Danielle Tenen, Daniel J. Wesche, Nadezhda Abazova, Max Hogue, Nilgun Tasdemir, Justin Brumbaugh, Philipp Rathert, Julian Jude, Francesco Ferrari, Andres Blanco, Michaela Fellner, Daniel Wenzel, Marietta Zinner, Simon E. Vidal, Oliver Bell, Matthias Stadtfeld, Howard Y. Chang, Genevieve Almouzni, Scott W. Lowe, John Rinn, Marius Wernig, Alexei Aravin, Yang Shi, Peter J. Park, Josef M. Penninger, Johannes Zuber, Konrad Hochedlinger

ABSTRACT

Cellular differentiation involves profound remodelling of chromatic landscapes, yet the mechanisms by which somatic cell identity is subsequently maintained remain incompletely understood. To further elucidate regulatory pathways that safeguard the somatic state, we performed two comprehensive RNA interference (RNAi) screens targeting chromatin factors during transcription-factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPS cells). Subunits of the chromatin assembly factor-1 (CAF-1) complex, including Chaf1a and Chaf1b, emerged as the most prominent hits from both screens, followed by modulators of lysine sumoylation and heterochromatin maintenance. Optimal modulation of both CAF-1 and transcription factor levels increased reprogramming efficiency by several orders of magnitude and facilitated iPS cell formation in as little as 4 days. Mechanistically, CAF-1 suppression led to a more accessible chromatin structure at enhancer elements early during reprogramming. These changes were accompanied by a decrease in somatic heterochromatin domains, increased binding of Sox2 to pluripotency-specific targets and activation of associated genes. Notably, suppression of CAF-1 also enhanced the direct conversion of B cells into macrophages and fibroblasts into neurons. Together, our findings reveal the histone chaperone CAF-1 to be a novel regulator of somatic cell identity during transcription-factor-induced cell-fate transitions and provide a potential strategy to modulate cellular plasticity in a regenerative setting. More... »

PAGES

218

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature15749

DOI

http://dx.doi.org/10.1038/nature15749

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052739043

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26659182


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nature15749'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nature15749'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature15749'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature15749'


 

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