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CpG island turnover events predict evolutionary changes in enhancer activity

Authors :
Kocher, Acadia A.
Dutrow, Emily V.
Uebbing, Severin
Yim, Kristina M.
Larios, María F. Rosales
Baumgartner, Marybeth
Nottoli, Timothy
Noonan, James
Kocher, Acadia A.
Dutrow, Emily V.
Uebbing, Severin
Yim, Kristina M.
Larios, María F. Rosales
Baumgartner, Marybeth
Nottoli, Timothy
Noonan, James
Source :
Genome Biology vol.25 (2024) date: 2024-06-12 nr.1 [ISSN 1465-6906]
Publication Year :
2024

Abstract

Background Genetic changes that modify the function of transcriptional enhancers have been linked to the evolution of biological diversity across species. Multiple studies have focused on the role of nucleotide substitutions, transposition, and insertions and deletions in altering enhancer function. CpG islands (CGIs) have recently been shown to influence enhancer activity, and here we test how their turnover across species contributes to enhancer evolution. Results We integrate maps of CGIs and enhancer activity-associated histone modifications obtained from multiple tissues in nine mammalian species and find that CGI content in enhancers is strongly associated with increased histone modification levels. CGIs show widespread turnover across species and species-specific CGIs are strongly enriched for enhancers exhibiting species-specific activity across all tissues and species. Genes associated with enhancers with species-specific CGIs show concordant biases in their expression, supporting that CGI turnover contributes to gene regulatory innovation. Our results also implicate CGI turnover in the evolution of Human Gain Enhancers (HGEs), which show increased activity in human embryonic development and may have contributed to the evolution of uniquely human traits. Using a humanized mouse model, we show that a highly conserved HGE with a large CGI absent from the mouse ortholog shows increased activity at the human CGI in the humanized mouse diencephalon. Conclusions Collectively, our results point to CGI turnover as a mechanism driving gene regulatory changes potentially underlying trait evolution in mammals.

Details

Database :
OAIster
Journal :
Genome Biology vol.25 (2024) date: 2024-06-12 nr.1 [ISSN 1465-6906]
Notes :
DOI: 10.1186/s13059-024-03300-z, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1445835964
Document Type :
Electronic Resource