Related Experiment Video
Updated: Aug 8, 2026
09:32
Deciphering High-Resolution 3D Chromatin Organization via Capture Hi-C
Published on: October 14, 2022
Haplotype-resolved DiMeLo-seq maps centromeric chromatin in a complete diploid human genome
Yuan Xu1, Hailey Loucks1, Julian Menendez1
1Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Cell Genomics
|August 6, 2026
Summary
Centromeres ensure chromosome segregation via centromere protein A (CENP-A) within repetitive DNA. This study reveals CENP-A subdomains and how cell culture affects centromere organization and DNA methylation.
Area of Science:
- Genomics
- Epigenetics
- Molecular Biology
Background:
- Centromeres are crucial for chromosome segregation but their organization within repetitive alpha-satellite DNA remains unclear.
- Understanding centromere chromatin is vital for studying genetic stability and diseases.
Purpose of the Study:
- To investigate the chromatin organization of human centromeres at a haplotype-resolved level.
- To explore the impact of cell culture conditions on centromere structure and epigenetic modifications.
Main Methods:
- Generated haplotype-resolved satellite DNA annotations for the T2T-HG002 human genome.
- Mapped centromere protein A (CENP-A), H3K9me3, and CpG methylation using directed methylation with long-read sequencing (DiMeLo-seq).
Main Results:
- Identified discrete CENP-A subdomains within hypomethylated centromere dip regions (CDRs).
- Demonstrated balanced CENP-A dosage between homologous chromosomes despite satellite array variation.
- Observed remodeling of DNA methylation and CENP-A organization upon cell culture and iPSC reprogramming.
Conclusions:
- Established a single-molecule, haplotype-resolved framework for studying human centromere plasticity.
- Highlighted the dynamic nature of centromere organization and epigenetic inheritance.
- Provided insights into factors influencing chromosomal instability in development and disease.
Related Concept Videos
02:30Histone Variants at the Centromere
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3 variants are also...
01:17Karyotyping
Describing the number and physical features of chromosomes can reveal abnormalities that underlie genetic diseases. This description is facilitated by special staining techniques that produce a particular banding pattern on each chromosome. State-of-the-art techniques make this approach even more powerful, enabling the detection of individual genes that cause disease.A Simple Chromosome Staining Technique Provides Valuable Scientific InsightSome genetic diseases can be detected by looking at...
02:40Chromosome Structure
A functional eukaryotic chromosome must contain three elements: a centromere, telomeres, and numerous origins of replication.
The centromere is a DNA sequence that links sister chromatids. This is also where kinetochores, protein complexes to which spindle microtubules attach, are constructed after the chromosome is replicated. The kinetochores allow the spindle microtubules to move the chromosomes within the cell during cell division.
Telomeres consist of non-coding repetitive nucleotide...
The centromere is a DNA sequence that links sister chromatids. This is also where kinetochores, protein complexes to which spindle microtubules attach, are constructed after the chromosome is replicated. The kinetochores allow the spindle microtubules to move the chromosomes within the cell during cell division.
Telomeres consist of non-coding repetitive nucleotide...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
02:04Polytene Chromosomes
Polytene chromosomes are giant interphase chromosomes with several DNA strands placed side by side. They were discovered in the year 1881 by Balbiani in salivary glands, intestine, muscles, malpighian tubules, and hypoderm of larvae Chironomus plumosus. Hence, these are also called "Salivary gland chromosomes." These are found in insects of the order Diptera and Collembola; in certain organs of mammals; and synergids, antipodes of flowering plants. Polytene chromosomes are also regularly...