Chromatin activity identifies differential gene regulation across human ancestries.
Genome Biol
; 25(1): 21, 2024 01 15.
Article
en En
| MEDLINE
| ID: mdl-38225662
ABSTRACT
BACKGROUND:
Current evidence suggests that cis-regulatory elements controlling gene expression may be the predominant target of natural selection in humans and other species. Detecting selection acting on these elements is critical to understanding evolution but remains challenging because we do not know which mutations will affect gene regulation.RESULTS:
To address this, we devise an approach to search for lineage-specific selection on three critical steps in transcriptional regulation chromatin activity, transcription factor binding, and chromosomal looping. Applying this approach to lymphoblastoid cells from 831 individuals of either European or African descent, we find strong signals of differential chromatin activity linked to gene expression differences between ancestries in numerous contexts, but no evidence of functional differences in chromosomal looping. Moreover, we show that enhancers rather than promoters display the strongest signs of selection associated with sites of differential transcription factor binding.CONCLUSIONS:
Overall, our study indicates that some cis-regulatory adaptation may be more easily detected at the level of chromatin than DNA sequence. This work provides a vast resource of genomic interaction data from diverse human populations and establishes a novel selection test that will benefit future study of regulatory evolution in humans and other species.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cromatina
/
Elementos de Facilitación Genéticos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Genome Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido