Impaired cell fate through gain-of-function mutations in a chromatin reader.

ABSTRACT: Modifications of histone proteins have essential roles in normal development and human disease. Recognition of modified histones by 'reader' proteins is a key mechanism that mediates the function of histone modifications, but how the dysregulation of these readers might contribute to disease remains poorly understood. We previously identified the ENL protein as a reader of histone acetylation via its YEATS domain, linking it to the expression of cancer-driving genes in acute leukaemia¹. Recurrent hotspot mutations have been found in the ENL YEATS domain in Wilms tumour^2,3, the most common type of paediatric kidney cancer. Here we show, using human and mouse cells, that these mutations impair cell-fate regulation by conferring gain-of-function in chromatin recruitment

SUBMITTER: Wan L 

PROVIDER: S-EPMC7061414 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature