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Related Concept Videos

Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Lineage Commitment01:21

Lineage Commitment

Commitment is the  process whereby stem cells:
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,...
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,...

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Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
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Epigenetic mechanisms in leukemia.

Sayyed K Zaidi1, Daniel J Trombly, Christopher R Dowdy

  • 1Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, 55 Lake Ave. N., Worcester, MA 01655, USA.

Advances in Biological Regulation
|August 14, 2012
PubMed
Summary

Runx proteins organize nuclear gene expression and epigenetic regulation. In cancer, leukemia proteins disrupt this organization, leading to disease progression and offering potential therapeutic targets.

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Published on: February 24, 2015

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Biology

Background:

  • Nuclear organization of regulatory machinery influences biological responsiveness and is altered in cancer.
  • Runx proteins are lineage determinants that organize transcription complexes and regulate gene expression via RNA polymerase II and I.
  • Runx proteins epigenetically control transcriptional programs, including nuclear architecture, mitotic bookmarking, and microRNA-mediated translation.

Purpose of the Study:

  • To investigate the role of Runx proteins in nuclear organization and gene regulation.
  • To understand how oncogenic proteins like AML1-ETO disrupt Runx-mediated mechanisms in acute myeloid leukemia.
  • To explore the potential of targeting the epigenetic landscape in leukemic cells.

Main Methods:

  • Analysis of Runx protein function in nuclear organization and gene expression.
  • Investigation of AML1-ETO protein's impact on Runx1 subnuclear localization and transcriptional regulation.
  • Epigenetic analysis, including chromatin modification and microRNA profiling in leukemic cells.

Main Results:

  • Runx proteins establish focal organization of regulatory machinery in the interphase nucleus.
  • The oncogenic AML1-ETO protein disrupts Runx1 localization and transcriptional control in acute myeloid leukemia.
  • AML1-ETO redirects Runx1, alters chromatin accessibility, and deregulates microRNA profiles, leading to leukemic cell phenotype maintenance.

Conclusions:

  • Runx proteins are critical for maintaining normal cellular function through epigenetic and transcriptional regulation.
  • Disruption of Runx-mediated mechanisms by oncogenic proteins drives acute myeloid leukemia.
  • The altered epigenetic landscape in leukemic cells presents a promising therapeutic avenue.