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Differential 3D genome architecture and imprinted gene expression: cause or consequence?
Benoit Moindrot1, Yui Imaizumi2, Robert Feil2
1Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France.
Imprinted genes link genome architecture and gene expression. Differential chromatin looping, driven by DNA methylation and CTCF binding, establishes parental allele-specific expression early in development.
Area of Science:
- Genomics
- Epigenetics
- Developmental Biology
Background:
- Imprinted genes exhibit parental allele-specific expression, crucial for development.
- Their regulation involves parental methylation imprints at regulatory DNA sequences within chromosomal domains.
- Understanding the interplay between genome architecture and imprinted gene expression is key.
Purpose of the Study:
- To explore the relationship between genome architecture and imprinted gene expression.
- To investigate how differential chromatin organization facilitates allele-specific transcription.
- To examine the reciprocal influence of gene expression on genome organization.
Main Methods:
- Chromatin conformation capture (3C)-based studies.
- Analysis of topologically associating domains (TADs) in imprinted regions.
- Investigation of CTCF and cohesin binding patterns at differentially methylated regions.
Main Results:
- Differential organization of TADs between parental chromosomes at imprinted domains.
- Allelic binding of CTCF and cohesin at the non-methylated allele.
- Generation of differential chromatin looping facilitating allelic gene expression.
- Evidence for reciprocal influence where transcription affects genome organization.
Conclusions:
- Epigenetically controlled differential genome architecture precedes and facilitates imprinted gene expression.
- Mono-allelic gene expression can also influence genome architecture at certain imprinted domains.
- This dynamic interplay is fundamental to developmental processes.

