Related Experiment Video
Updated: May 12, 2026

13:55
Combined Immunofluorescence and DNA FISH on 3D-preserved Interphase Nuclei to Study Changes in 3D Nuclear Organization
Published on: February 3, 2013
Bimodal quantitative relationships between histone modifications for X-linked and autosomal loci
Ruslan I Sadreyev1, Eda Yildirim, Stefan F Pinter
1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Summary
Histone modifications like H3K4me3 and H3K27me3 show complex, bimodal patterns during embryonic stem cell differentiation, challenging simple models of gene regulation and X-chromosome inactivation.
Area of Science:
- Epigenetics
- Molecular Biology
- Developmental Biology
Background:
- Gene expression is regulated by epigenetic mechanisms, including histone modifications.
- Recurrent patterns of colocalized histone modifications are linked to gene expression states.
- Interrelationships between individual histone modifications remain largely unknown.
Purpose of the Study:
- To quantitatively analyze relationships between colocalized histone marks during embryonic stem cell (ESC) differentiation.
- To investigate the quantitative relationships between H3K4me3 and H3K27me3 modifications.
- To resolve gene bivalency and understand X-chromosome inactivation (XCI) mechanisms.
Main Methods:
- Quantitative analysis of colocalized histone modifications in ESCs.
- Analysis of autosomal and X-linked gene behavior.
- Allele-specific analysis of chromatin modifications during XCI.
Main Results:
- Autosomal gene modification densities follow bimodal patterns.
- H3K4me3 and H3K27me3 show an unexpected positive correlation at inactive promoters.
- Gene bivalency and XCI exhibit complex dynamics not fitting simple models.
Conclusions:
- Relationships between H3K4me3 and H3K27me3 are nontrivial and context-dependent.
- Gene bivalency during ESC differentiation has unique aspects.
- X-chromosome inactivation does not strictly follow autosomal gene regulation models.
Related Concept Videos
Heterochromatin
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...
Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Inheritance of Chromatin Structures
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
X-linked Traits
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.

