Hominoid-Specific Transposable Elements and KZFPs Facilitate Human Embryonic Genome Activation and Control Transcription in Naive Human ESCs.


Journal

Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472

Informations de publication

Date de publication:
02 05 2019
Historique:
received: 09 11 2018
revised: 04 02 2019
accepted: 12 03 2019
pubmed: 23 4 2019
medline: 17 7 2020
entrez: 23 4 2019
Statut: ppublish

Résumé

Expansion of transposable elements (TEs) coincides with evolutionary shifts in gene expression. TEs frequently harbor binding sites for transcriptional regulators, thus enabling coordinated genome-wide activation of species- and context-specific gene expression programs, but such regulation must be balanced against their genotoxic potential. Here, we show that Krüppel-associated box (KRAB)-containing zinc finger proteins (KZFPs) control the timely and pleiotropic activation of TE-derived transcriptional cis regulators during early embryogenesis. Evolutionarily recent SVA, HERVK, and HERVH TE subgroups contribute significantly to chromatin opening during human embryonic genome activation and are KLF-stimulated enhancers in naive human embryonic stem cells (hESCs). KZFPs of corresponding evolutionary ages are simultaneously induced and repress the transcriptional activity of these TEs. Finally, the same KZFP-controlled TE-based enhancers later serve as developmental and tissue-specific enhancers. Thus, by controlling the transcriptional impact of TEs during embryogenesis, KZFPs facilitate their genome-wide incorporation into transcriptional networks, thereby contributing to human genome regulation.

Identifiants

pubmed: 31006620
pii: S1934-5909(19)30111-0
doi: 10.1016/j.stem.2019.03.012
pmc: PMC6509360
pii:
doi:

Substances chimiques

Chromatin 0
DNA Transposable Elements 0
Kruppel-Like Transcription Factors 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

724-735.e5

Subventions

Organisme : European Research Council
ID : 268721
Pays : International
Organisme : European Research Council
ID : 694658
Pays : International
Organisme : NINDS NIH HHS
ID : R01 NS088538
Pays : United States
Organisme : NICHD NIH HHS
ID : R37 HD045022
Pays : United States

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Julien Pontis (J)

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

Evarist Planet (E)

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

Sandra Offner (S)

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

Priscilla Turelli (P)

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

Julien Duc (J)

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

Alexandre Coudray (A)

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

Thorold W Theunissen (TW)

Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.

Rudolf Jaenisch (R)

Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.

Didier Trono (D)

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: didier.trono@epfl.ch.

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