Human centromere genomics: now it's personal

Abstract

Advances in human genomics have accelerated studies in evolution, disease, and cellular regulation. However, centromere sequences, defining the chromosomal interface with spindle microtubules, remain largely absent from ongoing genomic studies and disconnected from functional, genome-wide analyses. This disparity results from the challenge of predicting the linear order of multi-megabase-sized regions that are composed almost entirely of nearidentical satellite DNA. Acknowledging these challenges, the field of human centromere genomics possesses the potential to rapidly advance given the availability of individual, or personalized, genome projects matched with the promise of long-read sequencing technologies. Here I review the current genomic model of human centromeres in consideration of those studies involving functional datasets that examine the role of sequence in centromere identity.

The Mi-2 Homolog Mit1 Actively Positions Nucleosomes within Heterochromatin To Suppress Transcription

“…Given the known association of Mi-2/NuRD with centromeres and implications in heterochromatin function (16,17,94), it will be interesting to determine whether NuRD repositions nucleosomes similarly in regions of mammalian centromeric heterochromatin, especially considering the repetitive AT-rich nature of these satellite sequences (95).…”

Noisy silence

“…42 Human centromeres comprise arrays of 171-bp α-satellite repeats that are surrounded by arrays of longer repetitive elements, including satellites II and III (Sat II and III) that are interspersed with unique sequence elements. 43 Centric and pericentric regions differ in chromatin structure, forming structurally distinct domains, both of which are required for kinetochore assembly and proper chromosome segregation. Centromere identity is epigenetically determined by a unique chromatin signature in the core region, containing the centromere-specific histone H3 variant CENP-A and a nucleoprotein complex containing other centromeric proteins.…”

Diversity and distribution of alpha satellite DNA in the genome of an Old World monkey: Cercopithecus solatus

“…In the so-called higher order repeat (HOR) organizational pattern, highly conserved repeat units (97–100% sequence identity), each made of multiple 171 bp monomers (up to more than 30), are found as an homogenized array that can extend over a multimegabase-sized region [2, 13, 21–23]. This organization is typically found as very long arrays of alpha satellites at the centromere core of all human chromosomes.…”