| First Author | Kim IS | Year | 2012 |
| Journal | Mol Cell | Volume | 46 |
| Issue | 3 | Pages | 260-73 |
| PubMed ID | 22516971 | Mgi Jnum | J:188023 |
| Mgi Id | MGI:5438906 | Doi | 10.1016/j.molcel.2012.03.021 |
| Citation | Kim IS, et al. (2012) Roles of Mis18alpha in epigenetic regulation of centromeric chromatin and CENP-A loading. Mol Cell 46(3):260-73 |
| abstractText | The Mis18 complex has been identified as a critical factor for the centromeric localization of a histone H3 variant, centromeric protein A (CENP-A), which is responsible for the specification of centromere identity in the chromosome. However, the functional role of Mis18 complex is largely unknown. Here, we generated Mis18alpha conditional knockout mice and found that Mis18alpha deficiency resulted in lethality at early embryonic stage with severe defects in chromosome segregation caused by mislocalization of CENP-A. Further, we demonstrate Mis18alpha's crucial role for epigenetic regulation of centromeric chromatin by reinforcing centromeric localization of DNMT3A/3B. Mis18alpha interacts with DNMT3A/3B, and this interaction is critical for maintaining DNA methylation and hence regulating epigenetic states of centromeric chromatin. Mis18alpha deficiency led to reduced DNA methylation, altered histone modifications, and uncontrolled noncoding transcripts in centromere region by decreased DNMT3A/3B enrichment. Together, our findings uncover the functional mechanism of Mis18alpha and its pivotal role in mammalian cell cycle. |
