The diversity of zinc-finger genes on human chromosome 19 provides an evolutionary mechanism for defense against inherited endogenous retroviruses

Cell Death and Differentiation
S LukicA J Levine

Abstract

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections of the germ line that can remain capable of replication within the host genome. In the soma, DNA methylation and repressive chromatin keep the majority of this parasitic DNA transcriptionally silent. However, it is unclear how the host organism adapts to recognize and silence novel invading retroviruses that enter the germ line. Krueppel-Associated Box (KRAB)-associated protein 1 (KAP1) is a transcriptional regulatory factor that drives the epigenetic repression of many different loci in mammalian genomes. Here, we use published experimental data to provide evidence that human KAP1 is recruited to endogenous retroviral DNA by KRAB-containing zinc-finger transcription factors (TFs). Many of these zinc-finger genes exist in clusters associated with human chromosome 19. We demonstrate that these clusters are located at hotspots for copy number variation (CNV), generating a large and continuing diversity of zinc-finger TFs with new generations. These zinc-finger genes possess a wide variety of DNA binding affinities, but their role as transcriptional repressors is conserved. We also perform a computational study of the different ERVs that invaded the human...Continue Reading

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Citations

Jan 29, 2016·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Robin A Weiss
Oct 7, 2014·Journal of Cellular Physiology·Claire Marchal, Benoit Miotto
Mar 10, 2016·Annual Review of Virology·Welkin E Johnson
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Jan 23, 2015·PLoS Genetics·Peter J ThompsonMatthew C Lorincz
Jun 23, 2019·Genome Biology and Evolution·Álvaro Perdomo-Sabogal, Katja Nowick
Dec 20, 2015·Immunological Reviews·Philipp Yu
Jul 1, 2017·Ecology Letters·Nicolas AlcalaSéverine Vuilleumier
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Dec 1, 2019·International Journal of Molecular Sciences·Olympia GianfrancescoJohn P Quinn
Feb 29, 2020·BMC Evolutionary Biology·R Alan HarrisJeffrey Rogers
Feb 8, 2019·Communications Biology·Alan Herbert
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Jul 17, 2020·Proceedings of the National Academy of Sciences of the United States of America·Tongguang WangAvindra Nath
Jan 12, 2020·Communications Biology·Alan Herbert
Apr 6, 2021·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Andrew D CalcinoMarco Gerdol

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Datasets Mentioned

BETA
GSM700353
GSM700355

Methods Mentioned

BETA
ChIP-seq
immunoprecipitation

Software Mentioned

Illumina Genome Analyzer Pipeline
UCSC genome browser
RepeatMasker

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