Human gene regulatory evolution is driven by the divergence of regulatory element function in both cis and trans.
Cell Genom
; 4(4): 100536, 2024 Apr 10.
Article
em En
| MEDLINE
| ID: mdl-38604126
ABSTRACT
Gene regulatory divergence between species can result from cis-acting local changes to regulatory element DNA sequences or global trans-acting changes to the regulatory environment. Understanding how these mechanisms drive regulatory evolution has been limited by challenges in identifying trans-acting changes. We present a comprehensive approach to directly identify cis- and trans-divergent regulatory elements between human and rhesus macaque lymphoblastoid cells using assay for transposase-accessible chromatin coupled to self-transcribing active regulatory region (ATAC-STARR) sequencing. In addition to thousands of cis changes, we discover an unexpected number (â¼10,000) of trans changes and show that cis and trans elements exhibit distinct patterns of sequence divergence and function. We further identify differentially expressed transcription factors that underlie â¼37% of trans differences and trace how cis changes can produce cascades of trans changes. Overall, we find that most divergent elements (67%) experienced changes in both cis and trans, revealing a substantial role for trans divergence-alone and together with cis changes-in regulatory differences between species.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sequências Reguladoras de Ácido Nucleico
/
Regulação da Expressão Gênica
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Genom
/
Cell genomics
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos