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Functional and mechanistic studies of XPC DNA-repair complex as transcriptional coactivator in embryonic stem cells

Claudia Cattoglio1, Elisa T Zhang1, Ivan Grubisic2

  • 1Department of Molecular and Cell Biology, Howard Hughes Medical Institute, Li Ka Shing Center for Biomedical and Health Sciences, California Institute of Regenerative Medicine Center of Excellence.

Proceedings of the National Academy of Sciences of the United States of America
|April 23, 2015
PubMed

Insights

The xeroderma pigmentosum C (XPC)-RAD23B-CETN2 complex acts as a stem cell coactivator, essential for OCT4/SOX2 gene activation in embryonic stem cells. This study reveals its genome-wide role and interaction mechanisms.

Area of Science:

  • Stem cell biology
  • Molecular genetics
  • DNA repair mechanisms

Background:

  • Embryonic stem cell (ESC) pluripotency is regulated by transcription factors like OCT4, SOX2, and NANOG.
  • Understanding these regulatory circuits is key for stem cell applications.
  • The DNA-repair complex XPC-RAD23B-CETN2 was recently identified as a stem cell coactivator (SCC).

Purpose of the Study:

  • To investigate the genome-wide function of the SCC in murine ESCs.
  • To map the binding regions of RAD23B.
  • To analyze transcriptional changes upon SCC depletion.

Main Methods:

  • Genome-wide mapping of RAD23B binding sites in ESCs.
  • Transcriptional profiling of SCC-depleted ESCs.
  • Co-immunoprecipitation assays to study protein interactions.

Main Results:

  • OCT4 and SOX2 recruit SCC to regulatory regions of pluripotency genes.
  • The XPC subunit is crucial for SCC interaction with OCT4 and SOX2.
  • SCC depletion significantly alters the transcriptional landscape of ESCs.

Conclusions:

  • The SCC plays a critical role in regulating pluripotency gene expression.
  • XPC is essential for mediating the interaction between SCC and OCT4/SOX2.
  • This research uncovers novel functions of the SCC in stem cell regulation.
Keywords:
ChIP-seqRNA-seqpluripotencyprotein–protein interactionstranscription

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