CENP-A: A Histone H3 Variant with Key Roles in Centromere Architecture in Healthy and Diseased States

Abstract

Centromeres are key architectural components of chromosomes. Here, we examine their construction, maintenance, and functionality. Focusing on the mammalian centromerespecific histone H3 variant, CENP-A, we highlight its co-evolution with both centromeric DNA and its chaperone, HJURP. We then consider CENP-A de novo deposition and the importance of centromeric DNA recently uncovered with the added value from new ultra-long-read sequencing. We next review how to ensure the maintenance of CENP-A at the centromere throughout the cell cycle. Finally, we discuss the impact of disrupting CENP-A regulation on cancer and cell fate.

The cell-cycle choreography of H3 variants shapes the genome

“… 110 Diffuse hemispheric glioma (DHG) 16 years H3.3G34R/V (15%) Giant cell tumors of bone (GCTB) 35 years H3.3G34W/L (92%) Chondroblastoma 21 years H3.3K36M (95%) Cancer (breast, liver, ovarian, colon, bone, gastric, prostate) adult CENP-A overexpression (44%) Renaud-Pageot et al., 100 Sharma et al., 111 and Jeffery et al. 112 These include microcephaly, 102 , 103 , 104 oncohistone cancers: diffuse intrinsic pontine glioma (DIPG), diffuse hemispheric glioma (DHG), giant cell tumors of bone (GCTB), chondroblastoma, 105 , 106 , 107 , 108 , 109 , 110 and cancers with CENP-A overexpression. 100 , 111 , 112 …”

“… 112 These include microcephaly, 102 , 103 , 104 oncohistone cancers: diffuse intrinsic pontine glioma (DIPG), diffuse hemispheric glioma (DHG), giant cell tumors of bone (GCTB), chondroblastoma, 105 , 106 , 107 , 108 , 109 , 110 and cancers with CENP-A overexpression. 100 , 111 , 112 …”