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Related Concept Videos

Chromatin Immunoprecipitation- ChIP02:36

Chromatin Immunoprecipitation- ChIP

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Chromatin immunoprecipitation, or ChIP, is an antibody-based technique used to identify sites on DNA that bind to transcription factors of interest or histone proteins. It also helps determine the type of histone modifications such as acetylation, phosphorylation, or methylation.
Types of ChIP
ChIP can be divided into two types - X-ChIP and N-ChIP. X-ChIP involves in vivo cross-linking of histones and regulatory proteins to DNA, fragmenting the DNA by sonication, and isolating the protein-DNA...
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Heterochromatin02:38

Heterochromatin

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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...
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Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

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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...
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Histone Modification02:32

Histone Modification

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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...
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Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
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Related Experiment Video

Updated: Aug 17, 2025

Mapping Genome-wide Accessible Chromatin in Primary Human T Lymphocytes by ATAC-Seq
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RefTM: reference-guided topic modeling of single-cell chromatin accessibility data.

Zheng Zhang1, Shengquan Chen2, Zhixiang Lin1

  • 1Department of Statistics in the Chinese University of Hong Kong.

Briefings in Bioinformatics
|December 13, 2022
PubMed
Summary

RefTM enhances single-cell chromatin accessibility (scCAS) data analysis by integrating reference datasets. This reference-guided topic modeling approach improves the identification of cell types and regulatory mechanisms from sparse, high-dimensional scCAS data.

Keywords:
Integrative analysisReference-guidedSingle-cell chromatin accessibilityTopic models

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Area of Science:

  • Genomics
  • Computational Biology
  • Epigenetics

Background:

  • Single-cell chromatin accessibility sequencing (scCAS) offers insights into cellular heterogeneity.
  • Analyzing scCAS data is challenging due to high dimensionality and sparsity.
  • Topic modeling and reference-guided approaches can aid scCAS data interpretation.

Purpose of the Study:

  • To develop a novel method for analyzing single-cell chromatin accessibility data.
  • To leverage existing bulk and single-cell data for improved scCAS analysis.
  • To enhance cell type identification and regulatory mechanism discovery.

Main Methods:

  • Introduced RefTM (Reference-guided Topic Modeling).
  • Utilized topic models for single-cell data analysis.
  • Simultaneously modeled shared and unique biological variations, and covariate effects.

Main Results:

  • RefTM integrates bulk chromatin accessibility and annotated scCAS data.
  • The method accounts for shared biological variation between reference and target data.
  • RefTM models unique biological variation within scCAS data and known covariate effects.

Conclusions:

  • RefTM provides a robust framework for analyzing scCAS data.
  • The approach facilitates deeper understanding of epigenetic landscapes at single-cell resolution.
  • Reference-guided topic modeling is effective for dissecting cellular heterogeneity.