Peter J Park

Publications (3)94.63 Total impact

• Article: Genome-wide Chromatin Interactions of the Nanog Locus in Pluripotency, Differentiation, and Reprogramming.

  Effie Apostolou, Francesco Ferrari, Ryan M Walsh, Ori Bar-Nur, Matthias Stadtfeld, Sihem Cheloufi, Hannah T Stuart, Jose M Polo, Toshiro K Ohsumi, Mark L Borowsky, Peter V Kharchenko, Peter J Park, Konrad Hochedlinger
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  ABSTRACT: The chromatin state of pluripotency genes has been studied extensively in embryonic stem cells (ESCs) and differentiated cells, but their potential interactions with other parts of the genome remain largely unexplored. Here, we identified a genome-wide, pluripotency-specific interaction network around the Nanog promoter by adapting circular chromosome conformation capture sequencing. This network was rearranged during differentiation and restored in induced pluripotent stem cells. A large fraction of Nanog-interacting loci were bound by Mediator or cohesin in pluripotent cells. Depletion of these proteins from ESCs resulted in a disruption of contacts and the acquisition of a differentiation-specific interaction pattern prior to obvious transcriptional and phenotypic changes. Similarly, the establishment of Nanog interactions during reprogramming often preceded transcriptional upregulation of associated genes, suggesting a causative link. Our results document a complex, pluripotency-specific chromatin "interactome" for Nanog and suggest a functional role for long-range genomic interactions in the maintenance and induction of pluripotency.
  Cell stem cell 05/2013; · 23.56 Impact Factor
• Article: Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells.

  Matthias Stadtfeld, Effie Apostolou, Francesco Ferrari, Jiho Choi, Ryan M Walsh, Taiping Chen, Steen S K Ooi, Sang Yong Kim, Timothy H Bestor, Toshi Shioda, Peter J Park, Konrad Hochedlinger
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  ABSTRACT: The generation of induced pluripotent stem cells (iPSCs) often results in aberrant epigenetic silencing of the imprinted Dlk1-Dio3 gene cluster, compromising the ability to generate entirely iPSC-derived adult mice ('all-iPSC mice'). Here, we show that reprogramming in the presence of ascorbic acid attenuates hypermethylation of Dlk1-Dio3 by enabling a chromatin configuration that interferes with binding of the de novo DNA methyltransferase Dnmt3a. This approach allowed us to generate all-iPSC mice from mature B cells, which have until now failed to support the development of exclusively iPSC-derived postnatal animals. Our data show that transcription factor-mediated reprogramming can endow a defined, terminally differentiated cell type with a developmental potential equivalent to that of embryonic stem cells. More generally, these findings indicate that culture conditions during cellular reprogramming can strongly influence the epigenetic and biological properties of the resultant iPSCs.
  Nature Genetics 03/2012; 44(4):398-405, S1-2. · 35.53 Impact Factor
• Article: Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells.

  Matthias Stadtfeld, Effie Apostolou, Francesco Ferrari, Jiho Choi, Ryan M Walsh, Taiping Chen, Steen S K Ooi, Sang Yong Kim, Timothy H Bestor, Toshi Shioda, Peter J Park, Konrad Hochedlinger
  Nature Genetics 01/2012; 44(7):831. · 35.53 Impact Factor