Z-DNA formation in promoters conserved between human and mouse are associated with increased transcription reinitiation rates.
Sci Rep
; 14(1): 17786, 2024 08 01.
Article
em En
| MEDLINE
| ID: mdl-39090226
ABSTRACT
A long-standing question concerns the role of Z-DNA in transcription. Here we use a deep learning approach DeepZ that predicts Z-flipons based on DNA sequence, structural properties of nucleotides and omics data. We examined Z-flipons that are conserved between human and mouse genomes after generating whole-genome Z-flipon maps and then validated them by orthogonal approaches based on high resolution chemical mapping of Z-DNA and the transformer algorithm Z-DNABERT. For human and mouse, we revealed similar pattern of transcription factors, chromatin remodelers, and histone marks associated with conserved Z-flipons. We found significant enrichment of Z-flipons in alternative and bidirectional promoters associated with neurogenesis genes. We show that conserved Z-flipons are associated with increased experimentally determined transcription reinitiation rates compared to promoters without Z-flipons, but without affecting elongation or pausing. Our findings support a model where Z-flipons engage Transcription Factor E and impact phenotype by enabling the reset of preinitiation complexes when active, and the suppression of gene expression when engaged by repressive chromatin complexes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Regiões Promotoras Genéticas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Federação Russa
País de publicação:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM