Chromodomain-helicase-DNA-binding protein 6 (CHD6)

Chromodomain-helicase-DNA-binding protein 6 (CHD6) is a large nuclear chromatin remodeling enzyme that uses ATP hydrolysis to alter chromatin structure and regulate gene expression. CHD6 is rapidly recruited and retained at sites of oxidative DNA damage in a manner dependent on both a poly(ADP-ribose)-dependent motif and chromodomain regions; it supports cell survival after oxidative stress by enabling proper transcriptional, signaling, and chromatin compaction responses. CHD6 also regulates antioxidant gene expression, limits reactive oxygen species persistence, and modulates the DNA damage signaling cascade, especially the ATM pathway. In cancer, CHD6 is upregulated in colorectal tumors, where it has a critical oncogenic role through direct regulation of Wnt and EGF signaling. Specifically, it interacts with TCF4 and β-catenin to facilitate transcription of mitochondrial inner membrane protein TMEM65, thereby promoting mitochondrial homeostasis, ATP production, and cancer cell survival and invasion. Targeting the CHD6 axis through Wnt or EGFR inhibition can constrain tumor growth. Loss of CHD6 is associated with increased oxidative and DNA damage, checkpoint hypersensitivity, and impaired cell growth.

Other names

Chromodomain helicase DNA binding protein 6CHD6KIAA1335RIGBATP-dependent helicase CHD6Radiation-induced gene B proteinFLJ22369dJ620E11.1

Inhibition of Wnt signaling, Inhibition of EGFR signaling, Disruption of CHD6-mediated transcriptional activation (via TMEM65 and Wnt/EGF signaling pathways)