Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm.
In previous studies using candidate gene approaches, low sperm count (oligospermia) has been associated with altered sperm mRNA content and DNA methylation in both imprinted and non-imprinted genes. We performed a genome-wide analysis of sperm DNA methylation and mRNA content to test for association...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2011-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3107223?pdf=render |
id |
doaj-c965e9bdd36d4f0cb912438f19e15d83 |
---|---|
record_format |
Article |
spelling |
doaj-c965e9bdd36d4f0cb912438f19e15d832020-11-24T21:33:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0166e2028010.1371/journal.pone.0020280Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm.Sara E PachecoE Andres HousemanBrock C ChristensenCarmen J MarsitKarl T KelseyMark SigmanKim BoekelheideIn previous studies using candidate gene approaches, low sperm count (oligospermia) has been associated with altered sperm mRNA content and DNA methylation in both imprinted and non-imprinted genes. We performed a genome-wide analysis of sperm DNA methylation and mRNA content to test for associations with sperm function.Sperm DNA and mRNA were isolated from 21 men with a range of semen parameters presenting to a tertiary male reproductive health clinic. DNA methylation was measured with the Illumina Infinium array at 27,578 CpG loci. Unsupervised clustering of methylation data differentiated the 21 sperm samples by their motility values. Recursively partitioned mixture modeling (RPMM) of methylation data resulted in four distinct methylation profiles that were significantly associated with sperm motility (P = 0.01). Linear models of microarray analysis (LIMMA) was performed based on motility and identified 9,189 CpG loci with significantly altered methylation (Q<0.05) in the low motility samples. In addition, the majority of these disrupted CpG loci (80%) were hypomethylated. Of the aberrantly methylated CpGs, 194 were associated with imprinted genes and were almost equally distributed into hypermethylated (predominantly paternally expressed) and hypomethylated (predominantly maternally expressed) groups. Sperm mRNA was measured with the Human Gene 1.0 ST Affymetrix GeneChip Array. LIMMA analysis identified 20 candidate transcripts as differentially present in low motility sperm, including HDAC1 (NCBI 3065), SIRT3 (NCBI 23410), and DNMT3A (NCBI 1788). There was a trend among altered expression of these epigenetic regulatory genes and RPMM DNA methylation class.Using integrative genome-wide approaches we identified CpG methylation profiles and mRNA alterations associated with low sperm motility.http://europepmc.org/articles/PMC3107223?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sara E Pacheco E Andres Houseman Brock C Christensen Carmen J Marsit Karl T Kelsey Mark Sigman Kim Boekelheide |
spellingShingle |
Sara E Pacheco E Andres Houseman Brock C Christensen Carmen J Marsit Karl T Kelsey Mark Sigman Kim Boekelheide Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm. PLoS ONE |
author_facet |
Sara E Pacheco E Andres Houseman Brock C Christensen Carmen J Marsit Karl T Kelsey Mark Sigman Kim Boekelheide |
author_sort |
Sara E Pacheco |
title |
Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm. |
title_short |
Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm. |
title_full |
Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm. |
title_fullStr |
Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm. |
title_full_unstemmed |
Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm. |
title_sort |
integrative dna methylation and gene expression analyses identify dna packaging and epigenetic regulatory genes associated with low motility sperm. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
In previous studies using candidate gene approaches, low sperm count (oligospermia) has been associated with altered sperm mRNA content and DNA methylation in both imprinted and non-imprinted genes. We performed a genome-wide analysis of sperm DNA methylation and mRNA content to test for associations with sperm function.Sperm DNA and mRNA were isolated from 21 men with a range of semen parameters presenting to a tertiary male reproductive health clinic. DNA methylation was measured with the Illumina Infinium array at 27,578 CpG loci. Unsupervised clustering of methylation data differentiated the 21 sperm samples by their motility values. Recursively partitioned mixture modeling (RPMM) of methylation data resulted in four distinct methylation profiles that were significantly associated with sperm motility (P = 0.01). Linear models of microarray analysis (LIMMA) was performed based on motility and identified 9,189 CpG loci with significantly altered methylation (Q<0.05) in the low motility samples. In addition, the majority of these disrupted CpG loci (80%) were hypomethylated. Of the aberrantly methylated CpGs, 194 were associated with imprinted genes and were almost equally distributed into hypermethylated (predominantly paternally expressed) and hypomethylated (predominantly maternally expressed) groups. Sperm mRNA was measured with the Human Gene 1.0 ST Affymetrix GeneChip Array. LIMMA analysis identified 20 candidate transcripts as differentially present in low motility sperm, including HDAC1 (NCBI 3065), SIRT3 (NCBI 23410), and DNMT3A (NCBI 1788). There was a trend among altered expression of these epigenetic regulatory genes and RPMM DNA methylation class.Using integrative genome-wide approaches we identified CpG methylation profiles and mRNA alterations associated with low sperm motility. |
url |
http://europepmc.org/articles/PMC3107223?pdf=render |
work_keys_str_mv |
AT saraepacheco integrativednamethylationandgeneexpressionanalysesidentifydnapackagingandepigeneticregulatorygenesassociatedwithlowmotilitysperm AT eandreshouseman integrativednamethylationandgeneexpressionanalysesidentifydnapackagingandepigeneticregulatorygenesassociatedwithlowmotilitysperm AT brockcchristensen integrativednamethylationandgeneexpressionanalysesidentifydnapackagingandepigeneticregulatorygenesassociatedwithlowmotilitysperm AT carmenjmarsit integrativednamethylationandgeneexpressionanalysesidentifydnapackagingandepigeneticregulatorygenesassociatedwithlowmotilitysperm AT karltkelsey integrativednamethylationandgeneexpressionanalysesidentifydnapackagingandepigeneticregulatorygenesassociatedwithlowmotilitysperm AT marksigman integrativednamethylationandgeneexpressionanalysesidentifydnapackagingandepigeneticregulatorygenesassociatedwithlowmotilitysperm AT kimboekelheide integrativednamethylationandgeneexpressionanalysesidentifydnapackagingandepigeneticregulatorygenesassociatedwithlowmotilitysperm |
_version_ |
1725954682981974016 |