Mono-allelic retrotransposon insertion addresses epigenetic transcriptional repression in human genome.
BACKGROUND
Retrotransposons have been extensively studied in plants and animals and have been shown to have an impact on human genome dynamics and evolution. Their ability to move within genomes gives retrotransposons to affect genome instability.


METHODS
we examined the polymorphic inserted AluYa5, evolutionary young Alu, in the progesterone receptor gene to determine the effects of Alu insertion on molecular environment. We used mono-allelic inserted cell lines which carry both Alu-present and Alu-absent alleles. To determine the epigenetic change and gene expression, we performed restriction enzyme digestion, Pyrosequencing, and Chromatin Immunoprecipitation.


RESULTS
We observed that the polymorphic insertion of evolutionally young Alu causes increasing levels of DNA methylation in the surrounding genomic area and generates inactive histone tail modifications. Consequently the Alu insertion deleteriously inactivates the neighboring gene expression.


CONCLUSIONS
The mono-allelic Alu insertion cell line clearly showed that polymorphic inserted repetitive elements cause the inactivation of neighboring gene expression, bringing aberrant epigenetic changes.
Jane Anne Nohl Division of Hematology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. hmbyun@hsph.harvard.edu
Hyang-Min
HM
Byun
Kyu
K
Heo
Kasey J
KJ
Mitchell
Allen S
AS
Yang
D000483:Alleles; D020087:Alu Elements / Q000235:genetics*; D002460:Cell Line; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D015894:Genome, Human; D042822:Genomic Instability; D006801:Humans; D011980:Receptors, Progesterone / Q000235:genetics; D014158:Transcription, Genetic
D011980:Receptors, Progesterone