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Methylation and expression analyses of Pallister-Killian syndrome reveal partial dosage compensation of tetrasomy 12p and hypomethylation of gene-poor regions on 12p.

Davidsson, Josef LU and Johansson, Bertil LU (2016) In Epigenetics 11(3). p.194-204
Abstract
To ascertain the epigenomic features, i.e., the methylation, non-coding RNA, and gene expression patterns, associated with gain of i(12p) in Pallister-Killian syndrome (PKS), we investigated single cell clones, harboring either disomy 12 or tetrasomy 12p, from a patient with PKS. The i(12p)-positive cells displayed a characteristic expression and methylation signature. Of all the genes on 12p, 13% were overexpressed, including the ATN1, COPS7A, and NECAP1 genes in 12p13.31, a region previously implicated in PKS. However, the median expression fold change (1.3) on 12p was lower than expected by tetrasomy 12p. Thus, partial dosage compensation occurs in cells with i(12p). The majority (89%) of the significantly deregulated genes were not... (More)
To ascertain the epigenomic features, i.e., the methylation, non-coding RNA, and gene expression patterns, associated with gain of i(12p) in Pallister-Killian syndrome (PKS), we investigated single cell clones, harboring either disomy 12 or tetrasomy 12p, from a patient with PKS. The i(12p)-positive cells displayed a characteristic expression and methylation signature. Of all the genes on 12p, 13% were overexpressed, including the ATN1, COPS7A, and NECAP1 genes in 12p13.31, a region previously implicated in PKS. However, the median expression fold change (1.3) on 12p was lower than expected by tetrasomy 12p. Thus, partial dosage compensation occurs in cells with i(12p). The majority (89%) of the significantly deregulated genes were not situated on 12p, indicating that global perturbation of gene expression is a key pathogenetic event in PKS. Three genes-ATP6V1G1 in 9q32, GMPS in 3q25.31, and TBX5 in 12q24.21-exhibited concomitant hypermethylation and decreased expression. The i(12p)-positive cells displayed global hypomethylation of gene-poor regions on 12p, a footprint previously associated with constitutional and acquired gains of whole chromosomes as well as with X-chromosome inactivation in females. We hypothesize that this non-genic hypomethylation is associated with chromatin processing that facilitates cellular adaptation to excess genetic material. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Epigenetics
volume
11
issue
3
pages
194 - 204
publisher
Landes Bioscience
external identifiers
  • pmid:26890086
  • scopus:84961392142
  • wos:000375387400003
ISSN
1559-2294
DOI
10.1080/15592294.2016.1146854
language
English
LU publication?
yes
id
e4545f11-fcca-422e-8307-a31e151cdeb0 (old id 8825115)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26890086?dopt=Abstract
date added to LUP
2016-03-03 13:06:31
date last changed
2017-01-01 03:07:29
@article{e4545f11-fcca-422e-8307-a31e151cdeb0,
  abstract     = {To ascertain the epigenomic features, i.e., the methylation, non-coding RNA, and gene expression patterns, associated with gain of i(12p) in Pallister-Killian syndrome (PKS), we investigated single cell clones, harboring either disomy 12 or tetrasomy 12p, from a patient with PKS. The i(12p)-positive cells displayed a characteristic expression and methylation signature. Of all the genes on 12p, 13% were overexpressed, including the ATN1, COPS7A, and NECAP1 genes in 12p13.31, a region previously implicated in PKS. However, the median expression fold change (1.3) on 12p was lower than expected by tetrasomy 12p. Thus, partial dosage compensation occurs in cells with i(12p). The majority (89%) of the significantly deregulated genes were not situated on 12p, indicating that global perturbation of gene expression is a key pathogenetic event in PKS. Three genes-ATP6V1G1 in 9q32, GMPS in 3q25.31, and TBX5 in 12q24.21-exhibited concomitant hypermethylation and decreased expression. The i(12p)-positive cells displayed global hypomethylation of gene-poor regions on 12p, a footprint previously associated with constitutional and acquired gains of whole chromosomes as well as with X-chromosome inactivation in females. We hypothesize that this non-genic hypomethylation is associated with chromatin processing that facilitates cellular adaptation to excess genetic material.},
  author       = {Davidsson, Josef and Johansson, Bertil},
  issn         = {1559-2294},
  language     = {eng},
  month        = {02},
  number       = {3},
  pages        = {194--204},
  publisher    = {Landes Bioscience},
  series       = {Epigenetics},
  title        = {Methylation and expression analyses of Pallister-Killian syndrome reveal partial dosage compensation of tetrasomy 12p and hypomethylation of gene-poor regions on 12p.},
  url          = {http://dx.doi.org/10.1080/15592294.2016.1146854},
  volume       = {11},
  year         = {2016},
}