Cell specific patterns of methylation in the human placenta

Grigoriu, A; Ferreira, José Carlos; Choufani, Sanaa; Baczyk, Dora; Kingdom, John; Weksberg, Rosanna

doi:10.4161/epi.6.3.14196

Cited by 67 publications

(50 citation statements)

References 32 publications

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“…Epigenetic modification of genes in placental trophoblasts has been reported in previous studies [41]. DNA methylation of some tumor-suppressor genes such as Maspin, RASSF1A, and adenomatous polyposis coli (APC) have been investigated in human placentas [42e44].…”

Section: Discussionmentioning

confidence: 99%

Laminin α4 (LAMA4) expression promotes trophoblast cell invasion, migration, and angiogenesis, and is lowered in preeclamptic placentas

Shan¹,

Zhang²,

Xiao³

et al. 2015

Placenta

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Section: Discussionmentioning

confidence: 99%

Laminin α4 (LAMA4) expression promotes trophoblast cell invasion, migration, and angiogenesis, and is lowered in preeclamptic placentas

Shan¹,

Zhang²,

Xiao³

et al. 2015

Placenta

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“…In fact, chorionic villi show 10% -25% less cytosine methylation than fetal tissues (Ehrlich et al 1982). As the villous trophoblast (derived from trophectoderm) is the predominant cell type present in the placenta throughout gestation (Grigoriu et al 2011;Peñaherrera et al 2012), its distinct DNA methylation profile may in part reflect the exemption of the trophoblast from this early reprogramming (Fig. 1).…”

Section: Global Hypomethylationmentioning

confidence: 99%

The Human Placental Methylome

Robinson

Price

2015

Cold Spring Harbor Perspectives in Medicine

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This review provides an overview of the unique features of DNA methylation in the human placenta. We discuss the importance of understanding placental development, structure, and function in the interpretation of DNA methylation data. Examples are given of how DNA methylation is important in regulating placental-specific gene expression, including monoallelic expression and X-chromosome inactivation in the placenta. We also discuss studies of global DNA methylation changes in the context of placental pathology and environmental exposures.

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“…Human placenta is known to have lower levels of global DNA methylation (1,(11)(12)(13)) but whether placental tissue shows lower methylation genome-wide or has PMDs is currently unknown since many studies focus on promoters, CpG islands, and repetitive elements (14). A few locus-specific microarray-based studies have found that genes with higher tissuespecific expression in placenta also have higher DNA methylation in their gene bodies (15,16).…”

mentioning

confidence: 99%

The human placenta methylome

Schroeder

Blair

Lott

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

272

303

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Tissue-specific DNA methylation is found at promoters, enhancers, and CpG islands but also over larger genomic regions. In most human tissues, the vast majority of the genome is highly methylated (>70%). Recently, sequencing of bisulfite-treated DNA (MethylCseq) has revealed large partially methylated domains (PMDs) in some human cell lines. PMDs cover up to 40% of the genome and are associated with gene repression and inactive chromatin marks. However, to date, only cultured cells and cancers have shown evidence for PMDs. Here, we performed MethylC-seq in full-term human placenta and demonstrate it is the first known normal tissue showing clear evidence of PMDs. We found that PMDs cover 37% of the placental genome, are stable throughout gestation and between individuals, and can be observed with lower sensitivity in Illumina 450K Infinium data. RNA-seq analysis confirmed that genes in PMDs are repressed in placenta. Using a hidden Markov model to map placental PMDs genome-wide and compare them to PMDs in other cell lines, we found that genes within placental PMDs have tissuespecific functions. For regulatory regions, methylation levels in promoter CpG islands are actually higher for genes within placental PMDs, despite the lower overall methylation of surrounding regions. Similar to PMDs, polycomb-regulated regions are hypomethylated but smaller and distinct from PMDs, with some being hypermethylated in placenta compared with other tissues. These results suggest that PMDs are a developmentally dynamic feature of the methylome that are relevant for understanding both normal development and cancer and may be of use as epigenetic biomarkers.epigenomics | hypomethylation

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Cell specific patterns of methylation in the human placenta

Cited by 67 publications

References 32 publications

Laminin α4 (LAMA4) expression promotes trophoblast cell invasion, migration, and angiogenesis, and is lowered in preeclamptic placentas

Laminin α4 (LAMA4) expression promotes trophoblast cell invasion, migration, and angiogenesis, and is lowered in preeclamptic placentas

The Human Placental Methylome

The human placenta methylome

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