Abstract:
:UTX is a chromatin modifier required for development and neural lineage specification, but how it controls these biological processes is unclear. To determine the molecular mechanisms of UTX, we identified novel UTX protein interaction partners. Here we show that UTX and 53BP1 directly interact and co-occupy promoters in human embryonic stem cells and differentiating neural progenitor cells. Human 53BP1 contains a UTX-binding site that diverges from its mouse homolog by 41%, and disruption of the 53BP1-UTX interaction abrogated human, but not mouse, neurogenesis in vitro. The 53BP1-UTX interaction is required to upregulate key neurodevelopmental genes during the differentiation of human embryonic stem cells into neurons or into cortical organoids. 53BP1 promotes UTX chromatin binding, and in turn H3K27 modifications and gene activation, at a subset of genomic regions, including neurogenic genes. Overall, our data suggest that the 53BP1-UTX interaction supports the activation of key genes required for human neurodevelopment.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Yang X,Xu B,Mulvey B,Evans M,Jordan S,Wang YD,Pagala V,Peng J,Fan Y,Patel A,Peng JCdoi
10.1038/s41593-018-0328-5subject
Has Abstractpub_date
2019-03-01 00:00:00pages
362-373issue
3eissn
1097-6256issn
1546-1726pii
10.1038/s41593-018-0328-5journal_volume
22pub_type
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