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Genetics talks to epigenetics? The interplay between sequence variants and chromatin structure.

Silvio Zaina¹, Elva L Pérez-Luque, Gertrud Lund

¹Department of Medical Research, Division of Health Sciences, Leon Campus, University of Guanajuato, Leon, Mexico;

Current Genomics

|February 3, 2011

Summary

Genetic and epigenetic mechanisms co-regulate gene transcription. Understanding their interplay is crucial for resolving genetic variant-phenotype associations and understanding disease outcomes.

Keywords:

Chromatin DNA methylation epigenetics genetic variant histone single nucleotide polymorphism.

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Area of Science:

Molecular Biology
Genetics
Epigenetics

Background:

Transcription is regulated by DNA sequence changes (genetic regulation) and chromatin structure (epigenetic regulation).
These mechanisms are fundamental to transcriptional regulation and likely co-regulate a substantial portion of the genome.
The interplay between genetic and epigenetic regulation is not fully understood.

Purpose of the Study:

To review recent data on the co-participation of genetic and epigenetic mechanisms in transcriptional regulation.
To discuss the implications of this crosstalk for understanding genetic variant-phenotype associations.
To provide mechanistic explanations for unexplained genotype-phenotype discrepancies.

Main Methods:

Review of recently published scientific literature.
Discussion of existing data and theoretical frameworks.
Analysis of implications for genetic variant-phenotype association studies.

Main Results:

Mutations can significantly impact local chromatin structure, influencing epigenetic patterns like DNA methylation and histone modifications.
Crosstalk between genetics and epigenetics can explain cases where genetic variants correlate with phenotype but are not in coding or promoter regions.
Understanding this interplay is key to resolving discrepancies in genetic variant-phenotype associations.

Conclusions:

The co-regulation of transcription by genetic and epigenetic mechanisms is a significant factor in genome regulation.
Elucidating these interactions is essential for advancing genetic variant-phenotype association studies and understanding disease.
This integrated approach offers potential explanations for complex genetic and disease outcomes.