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

Summary: 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...

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Main Authors: Yu Tao, Ming-Ren Yen, Tsotne Chitiashvili, Haruko Nakano, Rachel Kim, Linzi Hosohama, Yao Chang Tan, Atsushi Nakano, Pao-Yang Chen, Amander T. Clark
Format: Article
Language:English
Published: Elsevier 2018-01-01
Series:Stem Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671117305283
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author Yu Tao
Ming-Ren Yen
Tsotne Chitiashvili
Haruko Nakano
Rachel Kim
Linzi Hosohama
Yao Chang Tan
Atsushi Nakano
Pao-Yang Chen
Amander T. Clark
author_facet Yu Tao
Ming-Ren Yen
Tsotne Chitiashvili
Haruko Nakano
Rachel Kim
Linzi Hosohama
Yao Chang Tan
Atsushi Nakano
Pao-Yang Chen
Amander T. Clark
author_sort Yu Tao
collection DOAJ
description Summary: 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.
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spelling doaj.art-221e0a6328a54f74ba9b69c806cfa0382022-12-22T01:45:18ZengElsevierStem Cell Reports2213-67112018-01-0110124325610.1016/j.stemcr.2017.11.020TRIM28-Regulated Transposon Repression Is Required for Human Germline Competency and Not Primed or Naive Human PluripotencyYu Tao0Ming-Ren Yen1Tsotne Chitiashvili2Haruko Nakano3Rachel Kim4Linzi Hosohama5Yao Chang Tan6Atsushi Nakano7Pao-Yang Chen8Amander T. Clark9Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USAInstitute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, TaiwanDepartment 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, USADepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USAEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USADepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USADepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USADepartment 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, USAInstitute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan; Corresponding authorDepartment 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2213671117305283TRIM28human embryonic stem celltransposable elementimprinted genes
spellingShingle Yu Tao
Ming-Ren Yen
Tsotne Chitiashvili
Haruko Nakano
Rachel Kim
Linzi Hosohama
Yao Chang Tan
Atsushi Nakano
Pao-Yang Chen
Amander T. Clark
TRIM28-Regulated Transposon Repression Is Required for Human Germline Competency and Not Primed or Naive Human Pluripotency
Stem Cell Reports
TRIM28
human embryonic stem cell
transposable element
imprinted genes
title TRIM28-Regulated Transposon Repression Is Required for Human Germline Competency and Not Primed or Naive Human Pluripotency
title_full TRIM28-Regulated Transposon Repression Is Required for Human Germline Competency and Not Primed or Naive Human Pluripotency
title_fullStr TRIM28-Regulated Transposon Repression Is Required for Human Germline Competency and Not Primed or Naive Human Pluripotency
title_full_unstemmed TRIM28-Regulated Transposon Repression Is Required for Human Germline Competency and Not Primed or Naive Human Pluripotency
title_short TRIM28-Regulated Transposon Repression Is Required for Human Germline Competency and Not Primed or Naive Human Pluripotency
title_sort trim28 regulated transposon repression is required for human germline competency and not primed or naive human pluripotency
topic TRIM28
human embryonic stem cell
transposable element
imprinted genes
url http://www.sciencedirect.com/science/article/pii/S2213671117305283
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