ARID1A facilitates KRAS signaling-regulated enhancer activity in an AP1-dependent manner in colorectal cancer cells.

Madhobi SenXin WangFeda H HamdanJacobe RappJessica EggertRobyn Laura KosinskyFlorian WegwitzAna Patricia KutschatFereshteh S YounesiJochen GaedckeMarian GradeElisabeth HessmannArgyris PapantonisPhilipp StrӧbelSteven A Johnsen

Published in: Clinical epigenetics (2019)

We identify a previously unknown context-dependent tumor-supporting function of ARID1A in CRC downstream of KRAS signaling. Upon the loss of ARID1A in KRAS-mutated cells, enhancers that are co-occupied by ARID1A and the AP1 transcription factors become inactive, thereby leading to decreased target gene expression. Thus, targeting of the BAF complex in KRAS-mutated CRC may offer a unique, previously unknown, context-dependent therapeutic option in CRC.

Keyphrases

wild type
transcription factor
gene expression
induced apoptosis
dna methylation
dna binding
binding protein
cancer therapy
genome wide identification