| First Author | Gao Y | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 2 | Pages | 103742 |
| PubMed ID | 35128353 | Mgi Jnum | J:326928 |
| Mgi Id | MGI:6870380 | Doi | 10.1016/j.isci.2022.103742 |
| Citation | Gao Y, et al. (2022) Impaired KDM2B-mediated PRC1 recruitment to chromatin causes defective neural stem cell self-renewal and ASD/ID-like behaviors. iScience 25(2):103742 |
| abstractText | 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. |
