Primate-specific Transposable Elements Shape Transcriptional Networks During Human Development

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Nov 23

PMID 36418324

Authors

Julien Pontis

Cyril Pulver

Christopher J Playfoot

Evarist Planet

Delphine Grun

Sandra Offner

Julien Duc

Andrea Manfrin

Matthias P Lutolf

Didier Trono

Affiliations

Soon will be listed here.

Abstract

The human genome contains more than 4.5 million inserts derived from transposable elements (TEs), the result of recurrent waves of invasion and internal propagation throughout evolution. For new TE copies to be inherited, they must become integrated in the genome of the germline or pre-implantation embryo, which requires that their source TE be expressed at these stages. Accordingly, many TEs harbor DNA binding sites for the pluripotency factors OCT4, NANOG, SOX2, and KLFs and are transiently expressed during embryonic genome activation. Here, we describe how many primate-restricted TEs have additional binding sites for lineage-specific transcription factors driving their expression during human gastrulation and later steps of fetal development. These TE integrants serve as lineage-specific enhancers fostering the transcription, amongst other targets, of KRAB-zinc finger proteins (KZFPs) of comparable evolutionary age, which in turn corral the activity of TE-embedded regulatory sequences in a similarly lineage-restricted fashion. Thus, TEs and their KZFP controllers play broad roles in shaping transcriptional networks during early human development.

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