De novo LINE-1 retrotransposition in HepG2 cells preferentially targets gene poor regions of chromosome 13

Pasano Bojang; Mark J. Anderton; Ruth A. Roberts; Kenneth S. Ramos

doi:10.1016/j.ygeno.2014.07.001

De novo LINE-1 retrotransposition in HepG2 cells preferentially targets gene poor regions of chromosome 13

Pasano Bojang, Mark J. Anderton, Ruth A. Roberts, Kenneth S. Ramos

Medicine

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Long interspersed nuclear elements (Line-1 or L1s) account for ~17% of the human genome. While the majority of human L1s are inactive, ~80-100 elements remain retrotransposition competent and mobilize through RNA intermediates to different locations within the genome. De novo insertions of L1s account for polymorphic variation of the human genome and disruption of target loci at their new location. In the present study, fluorescence in situ hybridization and DNA sequencing were used to characterize retrotransposition profiles of L1^RP in cultured human HepG2 cells. While expression of synthetic L1^RP was associated with full-length and truncated insertions throughout the entire genome, a strong preference for gene-poor regions, such as those found in chromosome 13 was observed for full-length insertions. These findings shed light into L1 targeting mechanisms within the human genome and question the putative randomness of L1 retrotransposition.

Original language	English (US)
Pages (from-to)	96-104
Number of pages	9
Journal	Genomics
Volume	104
Issue number	2
DOIs	https://doi.org/10.1016/j.ygeno.2014.07.001
State	Published - Aug 2014

Keywords

Chromosome 13
Fluorescence in situ hybridization
HepG2
Long interspersed nuclear element-1 (Line-1/L1)
Retrotransposons

ASJC Scopus subject areas

Genetics

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10.1016/j.ygeno.2014.07.001

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title = "De novo LINE-1 retrotransposition in HepG2 cells preferentially targets gene poor regions of chromosome 13",

abstract = "Long interspersed nuclear elements (Line-1 or L1s) account for ~17% of the human genome. While the majority of human L1s are inactive, ~80-100 elements remain retrotransposition competent and mobilize through RNA intermediates to different locations within the genome. De novo insertions of L1s account for polymorphic variation of the human genome and disruption of target loci at their new location. In the present study, fluorescence in situ hybridization and DNA sequencing were used to characterize retrotransposition profiles of L1RP in cultured human HepG2 cells. While expression of synthetic L1RP was associated with full-length and truncated insertions throughout the entire genome, a strong preference for gene-poor regions, such as those found in chromosome 13 was observed for full-length insertions. These findings shed light into L1 targeting mechanisms within the human genome and question the putative randomness of L1 retrotransposition.",

keywords = "Chromosome 13, Fluorescence in situ hybridization, HepG2, Long interspersed nuclear element-1 (Line-1/L1), Retrotransposons",

author = "Pasano Bojang and Anderton, {Mark J.} and Roberts, {Ruth A.} and Ramos, {Kenneth S.}",

note = "Funding Information: This work was supported in part by grants from the National Institute of Environmental Health Sciences ( ES014443 and ES017274 ) and AstraZeneca to KSR. We thank Dr. Alexander Asamoah for his referral and Ms. Margaret Barch for her excellent technical assistance and helpful discussions regarding G-banding measurements. We also gratefully acknowledge the assistance provided by Dr. Bhagavatula Moorthy for his assistance with gDNA sequencing. ",

year = "2014",

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doi = "10.1016/j.ygeno.2014.07.001",

language = "English (US)",

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AU - Bojang, Pasano

AU - Anderton, Mark J.

AU - Roberts, Ruth A.

AU - Ramos, Kenneth S.

N1 - Funding Information: This work was supported in part by grants from the National Institute of Environmental Health Sciences ( ES014443 and ES017274 ) and AstraZeneca to KSR. We thank Dr. Alexander Asamoah for his referral and Ms. Margaret Barch for her excellent technical assistance and helpful discussions regarding G-banding measurements. We also gratefully acknowledge the assistance provided by Dr. Bhagavatula Moorthy for his assistance with gDNA sequencing.

PY - 2014/8

Y1 - 2014/8

N2 - Long interspersed nuclear elements (Line-1 or L1s) account for ~17% of the human genome. While the majority of human L1s are inactive, ~80-100 elements remain retrotransposition competent and mobilize through RNA intermediates to different locations within the genome. De novo insertions of L1s account for polymorphic variation of the human genome and disruption of target loci at their new location. In the present study, fluorescence in situ hybridization and DNA sequencing were used to characterize retrotransposition profiles of L1RP in cultured human HepG2 cells. While expression of synthetic L1RP was associated with full-length and truncated insertions throughout the entire genome, a strong preference for gene-poor regions, such as those found in chromosome 13 was observed for full-length insertions. These findings shed light into L1 targeting mechanisms within the human genome and question the putative randomness of L1 retrotransposition.

AB - Long interspersed nuclear elements (Line-1 or L1s) account for ~17% of the human genome. While the majority of human L1s are inactive, ~80-100 elements remain retrotransposition competent and mobilize through RNA intermediates to different locations within the genome. De novo insertions of L1s account for polymorphic variation of the human genome and disruption of target loci at their new location. In the present study, fluorescence in situ hybridization and DNA sequencing were used to characterize retrotransposition profiles of L1RP in cultured human HepG2 cells. While expression of synthetic L1RP was associated with full-length and truncated insertions throughout the entire genome, a strong preference for gene-poor regions, such as those found in chromosome 13 was observed for full-length insertions. These findings shed light into L1 targeting mechanisms within the human genome and question the putative randomness of L1 retrotransposition.

KW - Chromosome 13

KW - Fluorescence in situ hybridization

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KW - Long interspersed nuclear element-1 (Line-1/L1)

KW - Retrotransposons

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De novo LINE-1 retrotransposition in HepG2 cells preferentially targets gene poor regions of chromosome 13

Abstract

Keywords

ASJC Scopus subject areas

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