Characterizing the Cellular Role of PHF6

TL;DRAbstract

Defective chromatin remodeling proteins are associated with both germline and acquired human disease. PHF6 is encoded by an X-linked gene that is predominantly expressed in the brain and thymus. Structurally, PHF6 contains nuclear and nucleolar localization sequences as well as two ZaP domains, which bind dsDNA. Germline mutations in PHF6 are the cause of BFLS, an XLID, while somatic PHF6 mutations have been identified in T-ALL, AML, and CML. Indeed, screening of a pediatric cohort of nine T-ALL patients revealed a novel H329Q mutation. In a further clinical analysis, T-ALL onset occurred in a 9-year old male BFLS patient with an R342X mutation, suggesting that BFLS might be a cancer predisposition syndrome. To better understand its protein function, recombinant PHF6 was co-immunoprecipitated for a mass spectrometry based proteomic screen. Notably, PHF6 co-purified with multiple constituents of the NuRD complex, an important transcriptional regulator during embryogenesis and lineage co

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