Loading…
The Rhox gene cluster suppresses germline LINE1 transposition
Significance Long interspersed element class 1 ( LINE1 ) elements are transposable elements that comprise ∼20% of mammalian genomes. Their activity must be tightly controlled or genome integrity will be compromised, leading to DNA damage and cell death. Here, we report that several members of a rapi...
Saved in:
Published in: | Proceedings of the National Academy of Sciences - PNAS 2021-06, Vol.118 (23) |
---|---|
Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Significance
Long interspersed element class 1 (
LINE1
) elements are transposable elements that comprise ∼20% of mammalian genomes. Their activity must be tightly controlled or genome integrity will be compromised, leading to DNA damage and cell death. Here, we report that several members of a rapidly evolving X-linked homeobox gene cluster suppress
LINE1
transposition. One family member of this
Rhox
gene cluster—
Rhox10
—silences
LINE1
expression and transposition in the male germline when it is hypomethylated and thus highly susceptible to
LINE1
activation.
Rhox10
acts by driving the expression of
Piwil2
, which encodes a key component in the Piwi-interacting RNA pathway. The ability of
Rhox
genes to suppress
LINE1
elements is evolutionarily conserved and perturbed by mutation in infertility patients.
Transposable elements (TEs) are mobile sequences that engender widespread mutations and thus are a major hazard that must be silenced. The most abundant active class of TEs in mammalian genomes is long interspersed element class 1 (
LINE1
). Here, we report that
LINE1
transposition is suppressed in the male germline by transcription factors encoded by a rapidly evolving X-linked homeobox gene cluster.
LINE1
transposition is repressed by many members of this RHOX transcription factor family, including those with different patterns of expression during spermatogenesis. One family member—RHOX10—suppresses
LINE1
transposition during fetal development in vivo when the germline would otherwise be susceptible to
LINE1
activation because of epigenetic reprogramming. We provide evidence that RHOX10 suppresses LINE transposition by inducing
Piwil2
, which encodes a key component in the Piwi-interacting RNA pathway that protects against TEs. The ability of RHOX transcription factors to suppress
LINE1
is conserved in humans but is lost in
RHOXF2
mutants from several infertile human patients, raising the possibility that loss of
RHOXF2
causes human infertility by allowing uncontrolled
LINE1
expression in the germline. Together, our results support a model in which the
Rhox
gene cluster is in an evolutionary arms race with TEs, resulting in expansion of the
Rhox
gene cluster to suppress TEs in different biological contexts. |
---|---|
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.2024785118 |