CENP-N promotes the compaction of centromeric chromatin

Abstract

The histone variant CENP-A is the epigenetic determinant for the centromere, where it is interspersed with canonical H3 to form a specialized chromatin structure that nucleates the kinetochore. The arrangement of nucleosomes at the centromere into higher order structure is unknown. Here we demonstrate that the CENP-A interacting protein CENP-N promotes the stacking of CENP-A containing mono-nucleosomes and nucleosomal arrays through a previously undefined interaction between the α6 helix of CENP-N with the DNA of a neighboring nucleosome. We describe the cryoEM structures and biophysical characterization of such CENP-N mediated nucleosome stacks and nucleosomal arrays and demonstrate that this interaction is responsible for the formation of densely packed chromatin at the centromere in the cell. Our results provide first evidence that CENP-A, together with CENP-N, promotes specific chromatin higher order structure at the centromere.

CENP-B-mediated DNA loops regulate activity and stability of human centromeres

“…Centromere compaction mediated by CENP-B might facilitate bundling of CENP-A nucleosomes that are expected to be spaced between each other. In favor of this hypothesis, high-order centromeric structures of $100-300 nm containing several CENP-A nucleosomes were already observed (Andronov et al, 2019) where other centromeric proteins such as CENP-C (Melters et al, 2019) and CENP-N (Pentakota et al, 2017;Zhou et al, 2021) could provide additional nucleosome bridging. Here, we show that the CENP-B-mediated compaction of centromeric chromatin in interphase favors CENP-C recruitment and, overall, maintenance of centromere identity by possibly bridging several centromeric nucleosomes creating a special chromatin environment (Figures 6A-6C and 7).…”

Integrated bioinformatics combined with machine learning to analyze shared biomarkers and pathways in psoriasis and cervical squamous cell carcinoma

“…Interestingly, human papillomavirus was found to induce cervical cancer through UHRF1-mediated promoter methylation, suggesting that treatment targeting UHRF1 may inhibit cervical carcinogenesis through cell cycle arrest and apoptosis (74)(75)(76)(77). The mitochondrial protein CENP-N regulates normal chromosome segregation by recognizing histone H3 in filamentous nucleosomes and promoting densification of filamentous chromatin (78,79). In this study, CENPN expression was significantly elevated in both psoriasis and cervical cancer tissues compared to control samples, which could serve as a potential diagnostic indicator for identifying cervical cancer in psoriasis patients.…”

“…The pathophysiology of psoriasis involves abnormal activation of the autoimmune system, both intrinsic and acquired. This dysregulation is a key component of mechanisms that prevent and interfere with cancer (79). There exists a robust association between cancer and inflammation, with inflammation representing a paramount risk factor in the development of cancer, often accompanied by inflammation (80).…”