Related Experiment Video
Updated: May 12, 2026
10:41
An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
Published on: April 5, 2018
A tiered hidden Markov model characterizes multi-scale chromatin states
Jessica L Larson1, Curtis Huttenhower, John Quackenbush
1Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA. larsonj5@gene.com
Genomics
|April 11, 2013
Summary
A new tiered hidden Markov model reveals multi-scale chromatin organization. Domain-level states offer robust insights into chromatin regulation and complexity in human embryonic stem cells.
Area of Science:
- Genomics
- Computational Biology
- Epigenetics
Background:
- Characterizing chromatin states is crucial for understanding gene regulation.
- Existing computational methods struggle to model multi-scale epigenomic patterns.
Purpose of the Study:
- To develop a novel computational method for modeling multi-scale chromatin organization.
- To analyze ChIP-seq data from human embryonic stem cells to identify distinct chromatin states.
Main Methods:
- Developed a tiered hidden Markov model (HMM).
- Applied the HMM to ChIP-seq data from human embryonic stem cells.
- Identified bin-level and domain-level chromatin states.
Main Results:
- Discovered a two-tier chromatin structure with 15 bin-level states and 3 domain-level states.
- Domain-level states capture large-scale variations and are more robust than bin-level states.
- Identified active intergenic regions containing non-coding RNAs and pseudogenes.
Conclusions:
- The tiered HMM effectively models multi-scale chromatin organization.
- Domain-level states provide a more coherent view of chromatin structure.
- Revealed an additional layer of complexity in chromatin organization with implications for gene regulation.
Related Concept Videos
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...
02:38Heterochromatin
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...
01:01Euchromatin
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...
02:32Histone 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,...
02:25Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
02:32Position-effect Variegation
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.