Proteomics

Dataset Information

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CHD6 IP from human induced pluripotent stem cells LC-MS-MS


ABSTRACT: Members of the chromodomain-helicase-DNA binding (CHD) protein family are chromatin remodelers implicated in human pathologies, with CHD6 being one of its least studied members. We discovered a de novo CHD6 missense mutation in a patient clinically presenting the rare Hallermann-Streiff syndrome (HSS). We used genome editing to generate isogenic iPSC lines and model HSS in relevant cell types. By combining genomics with functional in vivo and in vitro assays, we show that CHD6 binds a cohort of autophagy and stress response genes across cell types. The HSS mutation affects CHD6 protein folding and impairs its ability to recruit co-remodelers in response to DNA damage or autophagy stimulation. This leads to accumulation of DNA damage burden and senescence-like phenotypes. We therefore uncovered a molecular mechanism explaining HSS onset via chromatin control of autophagic flux and genotoxic stress surveillance.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Pluripotent Stem Cell, Cell Culture

DISEASE(S): Hallermann-streiff Syndrome

SUBMITTER: Yulia Kargapolova  

LAB HEAD: Argyris Papantonis

PROVIDER: PXD024803 | Pride | 2021-03-20

REPOSITORIES: Pride

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