TRIM28-Regulated Transposon Repression Is Required for Human Germline Competency and Not Primed or Naive Human Pluripotency

Yu Tao; Ming-Ren Yen; Tsotne Chitiashvili; Haruko Nakano; Rachel Kim; Linzi Hosohama; Yao Chang Tan; Atsushi Nakano; Pao-Yang Chen; Amander T Clark

doi:10.1016/j.stemcr.2017.11.020

TRIM28-Regulated Transposon Repression Is Required for Human Germline Competency and Not Primed or Naive Human Pluripotency

Stem Cell Reports. 2018 Jan 9;10(1):243-256. doi: 10.1016/j.stemcr.2017.11.020. Epub 2017 Dec 28.

Authors

Affiliations

¹ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Institute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan.
³ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁶ Institute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan. Electronic address: paoyang@gate.sinica.edu.tw.
⁷ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: clarka@ucla.edu.

Abstract

Transition from primed to naive pluripotency is associated with dynamic changes in transposable element (TE) expression and demethylation of imprinting control regions (ICRs). In mouse, ICR methylation and TE expression are each regulated by TRIM28; however, the role of TRIM28 in humans is less clear. Here, we show that a null mutation in TRIM28 causes significant alterations in TE expression in both the naive and primed states of human pluripotency, and phenotypically this has limited effects on self-renewal, instead causing a loss of germline competency. Furthermore, we discovered that TRIM28 regulates paternal ICR methylation and chromatin accessibility in the primed state, with no effects on maternal ICRs. Taken together, our study shows that abnormal TE expression is tolerated by self-renewing human pluripotent cells, whereas germline competency is not.

Keywords: TRIM28; human embryonic stem cell; imprinted genes; transposable element.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
DNA Methylation*
DNA Transposable Elements*
Genomic Imprinting*
Humans
Mice
Mutation*
Pluripotent Stem Cells / cytology
Pluripotent Stem Cells / metabolism*
Tripartite Motif-Containing Protein 28 / genetics*
Tripartite Motif-Containing Protein 28 / metabolism

Substances

DNA Transposable Elements
TRIM28 protein, human
Tripartite Motif-Containing Protein 28

Abstract

Publication types

MeSH terms

Substances

Grants and funding