CENPC

Last update 08 May 2025

Basic Info

Synonyms

CENP-C, CENP-C 1, CENPC

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Introduction

Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPC recruits DNA methylation and DNMT3B to both centromeric and pericentromeric satellite repeats and regulates the histone code in these regions.

100 Clinical Results associated with CENPC

100 Translational Medicine associated with CENPC

0 Patents (Medical) associated with CENPC

392

Literatures (Medical) associated with CENPC

01 Dec 2025·Chromosoma

Towards identification of a holocentromere marker in the lepidopteran model Spodoptera frugiperda

Article

Author: Legeai, Fabrice ; d'Alençon, Emmanuelle ; Gamble, Sally ; Gimenez, Sylvie ; Eychenne, Magali

Some insects have holocentric chromosomes, with multiple kinetochores rather than a single centromere. They also lack the CENP-A and CENP-C proteins, suggesting a kinetochore assembly process different from that of monocentric chromosomes. The homolog of CENP-T was recently shown to bind silent chromatin and to play a key role in kinetochore assembly in Bombyx mori, but its role in other insects with holocentric chromosomes is unknown. We identified kinetochore genes and analyzed their expression in Spodoptera frugiperda. We silenced the kinetochore genes cenp-L, cenp-S, cenp-X and ndc80 and searched for chromosome segregation defects in Sf9 cells. All kinetochore genes except cenp-S were more strongly expressed in gonadal than in somatic tissues. Immunofluorescence microscopy and RT-qPCR demonstrated the effective silencing of the target genes by transfection with dsRNA. In Sf9 cells depleted of CENP-L and NDC80, immunofluorescence microscopy revealed increases in mitotic index and in the proportion of cells with unaligned chromosomes or multipolar spindles. The depletion of CENP-S and CENP-X had no effect on mitotic index and no division defects were observed. This suggests that CENP-L and NDC80 play key roles in chromosome segregation, whereas the functions of CENP-S and CENP-X remain unknown. We have begun to characterize the kinetochore proteins (CENP-L, CENP-S, CENP-X, NDC80), a prerequisite for holocentromere identification in S. frugiperda. This study also provides the first information about the role, in Lepidoptera, of CENP-L, a protein essential to the structure of the constitutive centromere-associated network in species with monocentric chromosomes.

01 Apr 2025·Life Science Alliance

High-resolution analysis of human centromeric chromatin

Article

Author: Rakshit, Tatini ; Sturgill, David ; Dalal, Yamini ; Melters, Daniël P ; Grigoryev, Sergei A ; Bui, Minh

Centromeres are marked by the centromere-specific histone H3 variant CENP-A/CENH3. Throughout the cell cycle, the constitutive centromere-associated network is bound to CENP-A chromatin, but how this protein network modifies CENP-A nucleosome conformations in vivo is unknown. Here, we purify endogenous centromeric chromatin associated with the CENP-C complex across the cell cycle and analyze the structures by single-molecule imaging and biochemical assays. CENP-C complex–bound chromatin was refractory to MNase digestion. The CENP-C complex increased in height throughout the cell cycle culminating in mitosis, and the smaller CENP-C complex corresponds to the dimensions of in vitro reconstituted constitutive centromere-associated network. In addition, we found two distinct CENP-A nucleosomal configurations; the taller variant was associated with the CENP-C complex. Finally, CENP-A mutants partially corrected CENP-C overexpression–induced centromeric transcription and mitotic defects. In all, our data support a working model in which CENP-C is critical in regulating centromere homeostasis by supporting a unique higher order structure of centromeric chromatin and altering the accessibility of the centromeric chromatin fiber for transcriptional machinery.

01 Apr 2025·Molecular Biology of the Cell

Independence of centromeric and pericentromeric chromatin stability on CCAN components

Article

Author: Biggs, Ronald J. ; Straight, Aaron F. ; Marko, John F. ; Hendrix, Eline ; Sundararajan, Kousik ; Sun, Mingxuan

The chromatin of the centromere provides the assembly site for the mitotic kinetochore that couples microtubule attachment and force production to chromosome movement in mitosis. The chromatin of the centromere is specified by nucleosomes containing the histone H3 variant, CENP-A. The constitutive centromeric-associated network (CCAN) and kinetochore are assembled on CENP-A chromatin to enable chromosome separation. CENP-A chromatin is surrounded by pericentromeric heterochromatin, which itself is bound by the sequence specific binding protein, CENP-B. We performed mechanical experiments on mitotic chromosomes while tracking CENP-A and CENP-B to observe the centromere's stiffness and the role of the CCAN. We degraded CENP-C and CENP-N containing auxin-inducible degrons, which we verified compromises the CCAN via observation of CENP-T loss. Chromosome stretching revealed that the CENP-A domain does not visibly stretch, even in the absence of CENP-C and/or CENP-N. Pericentromeric chromatin deforms upon force application, stretching ∼3-fold less than the entire chromosome. CENP-C and/or CENP-N loss has no impact on pericentromere stretching. Chromosome-disconnecting nuclease treatments showed no structural effects on CENP-A. Our experiments show that the core-centromeric chromatin is more resilient and likely mechanically disconnected from the underlying pericentromeric chromatin, while the pericentric chromatin is deformable yet stiffer than the chromosome arms.

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