Sustainable integrative cell biology: CENP-C is guilty by association

TL;DR

This paper explores how CENP-C, a centromere protein, is linked to other proteins through data reanalysis, revealing unexpected connections in cell biology.

Contribution

The study introduces a guilt-by-association approach using existing proteomic datasets to uncover novel protein correlations involving CENP-C.

Findings

CENP-C correlates with cohesin levels, confirming known associations.

CENP-C shows unexpected correlations with inner nuclear membrane proteins and NuMA.

The analysis expands the understanding of centromeric chromatin beyond chromosome segregation.

Abstract

In the 40 years since the discovery of the CENP proteins, many studies have examined the role of these proteins and their interactions with other chromosomal proteins of the centromere and beyond. Together, these studies have yielded vast amounts of sequencing and proteomics data. Typically, each study has focused on a single question and the majority of each dataset remains largely unexplored. Often the interesting details of publicly deposited data are left behind, buried in archives online, while more and more new data are generated. Reanalysing these databases can represent a new paradigm for investigating diverse biological pathways in unprecedented detail. Here, we explore two publicly available pan-cancer proteomic datasets to compare proteins whose abundance correlates with CENP proteins, with a particular focus on CENP-C. Our analysis confirms an expected link between CENP-C and cohesin levels but reveals a surprising and unexpected correlation between CENP-C and proteins of the inner nuclear membrane and the NuMA protein. This guilt-by-association analysis has the potential to identify proteins that act in common pathways but never associate or colocalize and may not even be expressed at the same time in cells. As an example, we show here that it can reveal unexpected links that expand our conception of centromeric chromatin beyond chromosome segregation.

The online version contains supplementary material available at 10.1007/s00412-025-00840-6.

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