Unknown

Dataset Information

0

Non-overlapping Control of Transcriptome by Promoter- and Super-Enhancer-Associated Dependencies in Multiple Myeloma.


ABSTRACT: The relationship between promoter proximal transcription factor-associated gene expression and super-enhancer-driven transcriptional programs are not well defined. However, their distinct genomic occupancy suggests a mechanism for specific and separable gene control. We explored the transcriptional and functional interrelationship between E2F transcription factors and BET transcriptional co-activators in multiple myeloma. We found that the transcription factor E2F1 and its heterodimerization partner DP1 represent a dependency in multiple myeloma cells. Global chromatin analysis reveals distinct regulatory axes for E2F and BETs, with E2F predominantly localized to active gene promoters of growth and/or proliferation genes and BETs disproportionately at enhancer-regulated tissue-specific genes. These two separate gene regulatory axes can be simultaneously targeted to impair the myeloma proliferative program, providing an important molecular mechanism for combination therapy. This study therefore suggests a sequestered cellular functional control that may be perturbed in cancer with potential for development of a promising therapeutic strategy.

SUBMITTER: Fulciniti M 

PROVIDER: S-EPMC6407615 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications


The relationship between promoter proximal transcription factor-associated gene expression and super-enhancer-driven transcriptional programs are not well defined. However, their distinct genomic occupancy suggests a mechanism for specific and separable gene control. We explored the transcriptional and functional interrelationship between E2F transcription factors and BET transcriptional co-activators in multiple myeloma. We found that the transcription factor E2F1 and its heterodimerization par  ...[more]

Similar Datasets

2017-04-26 | GSE80661 | GEO
| S-EPMC7744621 | biostudies-literature
| S-EPMC4018722 | biostudies-literature
2023-09-25 | GSE244003 | GEO
| S-EPMC6097138 | biostudies-literature
2023-09-25 | GSE244002 | GEO
2023-09-25 | GSE243990 | GEO
2023-09-25 | GSE243978 | GEO
2013-12-10 | E-GEOD-46663 | biostudies-arrayexpress
2021-02-16 | GSE145938 | GEO