Unknown

Dataset Information

0

Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas.


ABSTRACT: Uterine leiomyomas (fibroids) are a major source of gynecologic morbidity in reproductive age women and are characterized by the excessive deposition of a disorganized extracellular matrix, resulting in rigid benign tumors. Although down regulation of the transcription factor AP-1 is highly prevalent in leiomyomas, the functional consequence of AP-1 loss on gene transcription in uterine fibroids remains poorly understood. Using high-resolution ChIP-sequencing, promoter capture Hi-C, and RNA-sequencing of matched normal and leiomyoma tissues, here we show that modified enhancer architecture is a major driver of transcriptional dysregulation in MED12 mutant uterine leiomyomas. Furthermore, modifications in enhancer architecture are driven by the depletion of AP-1 occupancy on chromatin. Silencing of AP-1 subunits in primary myometrium cells leads to transcriptional dysregulation of extracellular matrix associated genes and partly recapitulates transcriptional and epigenetic changes observed in leiomyomas. These findings establish AP-1 driven aberrant enhancer regulation as an important mechanism of leiomyoma disease pathogenesis.

SUBMITTER: Moyo MB 

PROVIDER: S-EPMC7040020 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas.

Moyo Mthabisi B MB   Parker J Brandon JB   Chakravarti Debabrata D  

Nature communications 20200224 1


Uterine leiomyomas (fibroids) are a major source of gynecologic morbidity in reproductive age women and are characterized by the excessive deposition of a disorganized extracellular matrix, resulting in rigid benign tumors. Although down regulation of the transcription factor AP-1 is highly prevalent in leiomyomas, the functional consequence of AP-1 loss on gene transcription in uterine fibroids remains poorly understood. Using high-resolution ChIP-sequencing, promoter capture Hi-C, and RNA-sequ  ...[more]

Similar Datasets

2020-01-01 | GSE128242 | GEO
| PRJNA526890 | ENA
| S-EPMC5430741 | biostudies-literature
| S-EPMC4984459 | biostudies-literature
2011-08-26 | GSE30673 | GEO
| S-EPMC6302612 | biostudies-literature
| S-EPMC10561729 | biostudies-literature
| S-EPMC4007231 | biostudies-literature
| S-EPMC3299761 | biostudies-literature
| S-EPMC6128746 | biostudies-literature