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Related Concept Videos

Histone Modification02:32

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,...
Spreading of Chromatin Modifications02:25

Spreading 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...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

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...
Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for injury repair.

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Related Experiment Video

Updated: May 9, 2026

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

Chromatin-modifying enzymes as modulators of reprogramming.

Tamer T Onder1, Nergis Kara, Anne Cherry

  • 1Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.

Nature
|March 6, 2012
PubMed
Summary

Researchers identified specific chromatin-modifying enzymes that influence induced pluripotent stem cell (iPSC) generation. Inhibiting DOT1L, a histone methyltransferase, accelerated reprogramming and increased iPSC yield, offering a new strategy for efficient iPSC production.

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Last Updated: May 9, 2026

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Area of Science:

  • Epigenetics and Stem Cell Biology
  • Chromatin Modification and Gene Regulation
  • Cellular Reprogramming Mechanisms

Background:

  • Somatic cell reprogramming to induced pluripotent stem cells (iPSCs) involves extensive epigenetic remodeling.
  • The roles of specific chromatin-modifying enzymes in this process are not fully understood.
  • Identifying key regulators can optimize iPSC generation efficiency.

Purpose of the Study:

  • To investigate how chromatin-modifying enzymes impact the efficiency of induced pluripotent stem cell (iPSC) generation.
  • To identify specific enzymes that act as barriers or facilitators in the reprogramming process.
  • To explore strategies for enhancing iPSC production using targeted epigenetic modulation.

Main Methods:

  • Utilized short hairpin RNAs (shRNAs) to target genes in DNA and histone methylation pathways.
  • Assessed the effects of inhibiting various chromatin-modifying enzymes on iPSC generation efficiency.
  • Performed genome-wide analysis of H3K79 dimethylation (H3K79me2) distribution during reprogramming.

Main Results:

  • Inhibition of Polycomb Repressive Complex 1 and 2 components, including EZH2, reduced reprogramming efficiency.
  • Suppression of SUV39H1, YY1, and DOT1L enhanced reprogramming.
  • DOT1L inhibition accelerated reprogramming, increased iPSC yield, and substituted for KLF4 and c-Myc, correlating with increased NANOG and LIN28 levels.

Conclusions:

  • Specific chromatin-modifying enzymes play critical roles as barriers or facilitators in somatic cell reprogramming.
  • DOT1L inhibition emerges as a potent strategy to enhance iPSC generation efficiency and yield.
  • Targeting chromatin modification pathways offers a promising approach for improving iPSC production with fewer reprogramming factors.