Genomics

Dataset Information

0

Genome-wide characterization of BCL6/STAT5-switch target genes identifies reprogramming of DNA damage response as a novel branch of RAC1/PAK1 signalling


ABSTRACT: The RAC1 GTPase and its effector PAK1 have been found to be overexpressed or hyperactivated in colorectal cancer (CRC), one of the most prevalent types of cancer in the world. This overexpression frequently correlates with chemoresistance and less favourable prognoses. We previously showed that the activation of RAC1/PAK1 signalling promotes a switch between the BCL6 transcriptional repressor and the STAT5 transcriptional activator at a subset of pro-proliferative gene promoters. Here we used ChIP-Seq, under conditions of pathway inhibition and stimulation, to identify the BCL6/STAT5-switch binding sites throughout the genome. Using a knowledge-driven pipeline for ChIP-Seq data analysis, we identify 3774 genomic features associated to the switch-motif, with a significant enrichment in protein-coding genes involved in DNA damage repair pathways. Stimulation of RAC1/PAK1 signalling in DLD-1 CRC cells increased the expression of these genes and significantly enhanced DNA repair in response to damage induced by alkylating agents. Our results reveal a new transcriptional reprogramming mechanism whereby the alternate binding of a repressor and an activator protein to low-affinity motifs is used to coordinate a transcriptional response to DNA damage. This mechanism may link the upregulation of the RAC1/PAK1 pathway to the chemoresistant phenotype of aggressive CRCs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE97938 | GEO | 2019/04/30

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

| PRJNA383400 | ENA
2011-12-18 | E-GEOD-31578 | biostudies-arrayexpress
2024-12-01 | GSE247696 | GEO
2011-12-18 | GSE31578 | GEO
2024-09-25 | GSE239381 | GEO
2024-09-25 | GSE239306 | GEO
2024-06-03 | PXD044344 | Pride
2014-02-20 | E-GEOD-41317 | biostudies-arrayexpress
2024-06-23 | PXD050237 | Pride
2014-02-20 | GSE41317 | GEO