Promoter-Intrinsic and Local Chromatin Features Determine Gene Repression in LADs.
Cell
; 177(4): 852-864.e14, 2019 05 02.
Article
in En
| MEDLINE
| ID: mdl-30982597
ABSTRACT
It is largely unclear whether genes that are naturally embedded in lamina-associated domains (LADs) are inactive due to their chromatin environment or whether LADs are merely secondary to the lack of transcription. We show that hundreds of human promoters become active when moved from their native LAD position to a neutral context in the same cells, indicating that LADs form a repressive environment. Another set of promoters inside LADs is able to "escape" repression, although their transcription elongation is attenuated. By inserting reporters into thousands of genomic locations, we demonstrate that escaper promoters are intrinsically less sensitive to LAD repression. This is not simply explained by promoter strength but by the interplay between promoter sequence and local chromatin features that vary strongly across LADs. Enhancers also differ in their sensitivity to LAD chromatin. This work provides a general framework for the systematic understanding of gene regulation by repressive chromatin.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression Regulation
/
Promoter Regions, Genetic
/
Nuclear Lamina
Limits:
Humans
Language:
En
Journal:
Cell
Year:
2019
Type:
Article
Affiliation country:
Netherlands