Mots-Clés

enhancers promoters expression quantitative trait loci gene expression regulation genetic variants human genetics

Description

Genes are transcriptionnally regulated by a combination of distal gene regulatory sequences and proximal promoters. Our and other laboratories have shown that gene promoters also exert a distal transcriptional regulatory function, also called enhancer activity, on different distal genes (10.1038/ng.3884). These gene promoters with distal activity have been called enhancer-promoter (Epromoters). Genetic variants found in the non-coding genome and overlapping cis-regulatory elements have the potential to influence gene expression. Promoter eQTLs affect the expression of proximal and distal genes and might therefore be involved in multiple diseases. We have recently found that these proximal and distal effects correlate with the activity of classical promoters and Epromoters in lymphoblastoid cell lines (LCLs).

In this internship, we would like to compare these proximal and distal effects in enhancer regions in LCLs. We would also like to compare our observations in LCLs with other cell types and tissues. These integrative analyses might lead to a better understanding of how regulatory variants impact on gene expression.

References:

- Genome-wide characterization of mammalian promoters with distal enhancer functions. 2017. DOI:10.1038/ng.3884.
- The GTEx Consortium atlas of genetic regulatory effects across human tissues. 2020. DOI:10.1126/science.aaz1776.
- Enhancer histone-QTLs are enriched on autoimmune risk haplotypes and influence gene expression within chromatin networks. 2018. DOI 10.1038/s41467-018-05328-9
- Transcriptome and genome sequencing uncovers functional variation in humans. 2013. DOI:10.1038/nature12531
- Genetic Control of Chromatin States in Humans Involves Local and Distal Chromosomal Interactions. 2015. DOI:10.1016/j.cell.2015.07.048