Differentiation of human pluripotent stem cells into neurons or cortical organoids requires transcriptional co-regulation by UTX and 53BP1.

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 Neurosci

journal_title

Nature neuroscience

authors

Yang X,Xu B,Mulvey B,Evans M,Jordan S,Wang YD,Pagala V,Peng J,Fan Y,Patel A,Peng JC

doi

10.1038/s41593-018-0328-5

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

362-373

issue

3

eissn

1097-6256

issn

1546-1726

pii

10.1038/s41593-018-0328-5

journal_volume

22

pub_type

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