2022 journal article
Impaired KDM2B-mediated PRC1 recruitment to chromatin causes defective neural stem cell self-renewal and ASD/ID-like behaviors
IScience, 25(2), 103742.
TL;DR:
A critical role of KDM2B in normal brain development is revealed, a causality between the Kdm2b mutation and ASD/ID-like phenotypes in mice are revealed, and potential molecular mechanisms linking the function of K DM2B-PRC1 in transcriptional regulation to the 12q24.31 microdeletion-associated ASD/ ID are proposed.
(via Semantic Scholar)
open access via www.ncbi.nlm.nih.gov (repository)
Source: ORCID
Added: January 28, 2024
Recent clinical studies report that chromosomal 12q24.31 microdeletions are associated with autism spectrum disorder (ASD) and intellectual disability (ID). However, the causality and underlying mechanisms linking 12q24.31 microdeletions to ASD/ID remain undetermined. Here we show Kdm2b, one gene located in chromosomal 12q24.31, plays a critical role in maintaining neural stem cells (NSCs) in the mouse brain. Loss of the CxxC-ZF domain of KDM2B impairs its function in recruiting Polycomb repressive complex 1 (PRC1) to chromatin, resulting in de-repression of genes involved in cell apoptosis, cell-cycle arrest, NSC senescence, and loss of NSC populations in the brain. Of importance, the Kdm2b mutation is sufficient to induce ASD/ID-like behavioral and memory deficits. Thus, our study reveals a critical role of KDM2B in normal brain development, a causality between the Kdm2b mutation and ASD/ID-like phenotypes in mice, and potential molecular mechanisms linking the function of KDM2B-PRC1 in transcriptional regulation to the 12q24.31 microdeletion-associated ASD/ID.