Related Experiment Video
Updated: May 31, 2025
09:32
Deciphering High-Resolution 3D Chromatin Organization via Capture Hi-C
Published on: October 14, 2022
3.3K
High-resolution analysis of human centromeric chromatin.
Daniël P Melters1, Minh Bui2, Tatini Rakshit2,3
1National Cancer Institute, Center for Cancer Research, Laboratory of Receptor Biology and Gene Expression, Bethesda, MD, USA daniel.melters@nih.gov.
Life Science Alliance
|January 23, 2025
Summary
The CENP-C complex shapes centromeric chromatin structure, influencing centromere homeostasis and accessibility for transcription. This study reveals CENP-C
Area of Science:
- Cell Biology
- Epigenetics
- Chromatin Biology
Background:
- Centromeres are essential chromosomal regions for accurate cell division.
- The centromere-specific histone H3 variant CENP-A (also known as CENH3) marks centromeres.
- The constitutive centromere-associated network interacts with CENP-A chromatin throughout the cell cycle, but its structural impact is unclear.
Purpose of the Study:
- To investigate how the CENP-C complex modifies CENP-A nucleosome conformations in vivo.
- To elucidate the role of CENP-C in regulating centromeric chromatin structure and homeostasis.
Main Methods:
- Purification of endogenous centromeric chromatin associated with the CENP-C complex across the cell cycle.
- Single-molecule imaging and biochemical assays (MNase digestion).
- Analysis of CENP-A nucleosomal configurations and CENP-C complex dimensions.
Main Results:
- CENP-C complex-bound chromatin is resistant to MNase digestion.
- The size of the CENP-C complex increases throughout the cell cycle, peaking in mitosis.
- Two distinct CENP-A nucleosomal configurations were identified, with a taller variant associated with CENP-C.
- CENP-A mutants partially rescued defects caused by CENP-C overexpression.
Conclusions:
- CENP-C is crucial for maintaining centromere homeostasis.
- CENP-C supports a unique higher-order structure of centromeric chromatin.
- CENP-C alters the accessibility of centromeric chromatin to the transcriptional machinery.
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