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Mouse In Vivo Placental Targeted CRISPR Manipulation

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The human placenta methylome.

Diane I Schroeder¹, John D Blair, Paul Lott

¹Department of Medical Microbiology and Immunology, UC Davis School of Medicine, Davis, CA 95616, USA.

Proceedings of the National Academy of Sciences of the United States of America

|March 27, 2013

Summary

Partially methylated domains (PMDs) are newly identified in normal human placenta, revealing epigenetic regulation crucial for development. These large genomic regions are stable and associated with repressed genes, offering insights into normal development and cancer.

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Area of Science:

Epigenetics
Genomics
Developmental Biology

Background:

DNA methylation patterns vary across genomic regions like promoters and CpG islands.
Large partially methylated domains (PMDs) were previously identified only in cell lines and cancers.
PMDs are associated with gene repression and inactive chromatin.

Purpose of the Study:

To investigate the presence and characteristics of PMDs in normal human placenta.
To determine if PMDs are developmentally dynamic and functionally relevant in placental tissue.
To compare placental PMDs with those found in other cell types.

Main Methods:

Whole-genome bisulfite sequencing (MethylC-seq) was performed on human placenta.
RNA-sequencing (RNA-seq) was used to analyze gene expression.
A hidden Markov model was employed to map PMDs genome-wide.

Main Results:

The human placenta exhibits widespread PMDs, covering 37% of the genome, stable throughout gestation and across individuals.
Genes within placental PMDs are repressed, and these PMDs can be detected in lower-resolution array data.
Placental PMDs harbor genes with tissue-specific functions, and their promoter CpG islands show higher methylation.
Polycomb-regulated regions are distinct from PMDs and show tissue-specific methylation changes.

Conclusions:

The placenta is the first normal tissue identified with significant PMDs, indicating they are a dynamic feature of the methylome.
Placental PMDs are linked to developmental processes and gene repression.
PMDs represent a potential source of epigenetic biomarkers for normal development and cancer.