Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Stem Cells. 2017 Jan;35(1):147-157. doi: 10.1002/stem.2453. Epub 2016 Jul 6.

TRIM28 is an Epigenetic Barrier to Induced Pluripotent Stem Cell Reprogramming.

Author information

1
Division of Molecular Genetics, NKI Robotics and Screening Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
2
Division of Molecular Carcinogenesis, NKI Robotics and Screening Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
3
Division of Molecular of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
4
Cancer Genomics Centre (CGC.nl), Amsterdam, The Netherlands.

Abstract

Since the discovery of induced pluripotent stem cells there has been intense interest in understanding the mechanisms that allow a somatic cell to be reprogrammed back to a pluripotent state. Several groups have studied the alterations in gene expression that occur as somatic cells modify their genome to that of an embryonic stem cell. Underpinning many of the gene expression changes are modifications to the epigenetic profile of the associated chromatin. We have used a large-scale shRNA screen to identify epigenetic modifiers that act as barriers to reprogramming. We have uncovered an important role for TRIM28 in cells resisting transition between somatic and pluripotent states. TRIM28 achieves this by maintaining the H3K9me3 repressed state and keeping endogenous retroviruses (ERVs) silenced. We propose that knockdown of TRIM28 during reprogramming results in more plastic H3K9me3 domains, dysregulation of genes nearby H3K9me3 marks, and up regulation of ERVs, thus facilitating the transition through reprogramming. Stem Cells 2017;35:147-157.

KEYWORDS:

Epigenetics; Induced pluripotent stem cells; Reprogramming; Trim28

PMID:
27350605
DOI:
10.1002/stem.2453
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center