Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci.

Details

Serval ID
serval:BIB_D9CCA98B8DC1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci.
Journal
Nature genetics
Author(s)
Sungalee S., Liu Y., Lambuta R.A., Katanayeva N., Donaldson Collier M., Tavernari D., Roulland S., Ciriello G., Oricchio E.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
05/2021
Peer-reviewed
Oui
Volume
53
Number
5
Pages
650-662
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
In cancer cells, enhancer hijacking mediated by chromosomal alterations and/or increased deposition of acetylated histone H3 lysine 27 (H3K27ac) can support oncogene expression. However, how the chromatin conformation of enhancer-promoter interactions is affected by these events is unclear. In the present study, by comparing chromatin structure and H3K27ac levels in normal and lymphoma B cells, we show that enhancer-promoter-interacting regions assume different conformations according to the local abundance of H3K27ac. Genetic or pharmacological depletion of H3K27ac decreases the frequency and the spreading of these interactions, altering oncogene expression. Moreover, enhancer hijacking mediated by chromosomal translocations influences the epigenetic status of the regions flanking the breakpoint, prompting the formation of distinct intrachromosomal interactions in the two homologous chromosomes. These interactions are accompanied by allele-specific gene expression changes. Overall, our work indicates that H3K27ac dynamics modulates interaction frequency between regulatory regions and can lead to allele-specific chromatin configurations to sustain oncogene expression.
Pubmed
Create date
19/05/2021 14:30
Last modification date
07/07/2021 5:36
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