| First Author | Yoshida T | Year | 2019 |
| Journal | Genes Dev | Volume | 33 |
| Issue | 13-14 | Pages | 763-781 |
| PubMed ID | 31123064 | Mgi Jnum | J:284186 |
| Mgi Id | MGI:6390764 | Doi | 10.1101/gad.321901.118 |
| Citation | Yoshida T, et al. (2019) Chromatin restriction by the nucleosome remodeler Mi-2beta and functional interplay with lineage-specific transcription regulators control B-cell differentiation. Genes Dev 33(13-14):763-781 |
| abstractText | Coordinated induction, but also repression, of genes are key to normal differentiation. Although the role of lineage-specific transcription regulators has been studied extensively, their functional integration with chromatin remodelers, one of the key enzymatic machineries that control chromatin accessibility, remains ill-defined. Here we investigate the role of Mi-2beta, a SNF-2-like nucleosome remodeler and key component of the nucleosome remodeling and histone deacetylase (NuRD) complex in early B cells. Inactivation of Mi-2beta arrested differentiation at the large pre-B-cell stage and caused derepression of cell adhesion and cell migration signaling factors by increasing chromatin access at poised enhancers and chromosome architectural elements. Mi-2beta also supported IL-7R signaling, survival, and proliferation by repressing negative effectors of this pathway. Importantly, overexpression of Bcl2, a mitochondrial prosurvival gene and target of IL-7R signaling, partly rescued the differentiation block caused by Mi-2beta loss. Mi-2beta stably associated with chromatin sites that harbor binding motifs for IKAROS and EBF1 and physically associated with these transcription factors both on and off chromatin. Notably, Mi-2beta shared loss-of-function cellular and molecular phenotypes with IKAROS and EBF1, albeit in a distinct fashion. Thus, the nucleosome remodeler Mi-2beta promotes pre-B-cell differentiation by providing repression capabilities to distinct lineage-specific transcription factor-based regulatory networks. |
