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Related Concept Videos

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
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Heterochromatin02:38

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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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Heterochromatin

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Euchromatin01:01

Euchromatin

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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 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.
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Master Transcription Regulators02:23

Master Transcription Regulators

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Mdm2 as a chromatin modifier.

Magdalena Wienken1, Ute M Moll1,2, Matthias Dobbelstein1

  • 1Institute of Molecular Oncology, Göttingen Center for Molecular Biosciences (GZMB), University Medical Center Göttingen, Göttingen 37077, Germany.

Journal of Molecular Cell Biology
|December 9, 2016
PubMed
Summary
This summary is machine-generated.

Mdm2 regulates gene expression and cell stemness independently of p53 by interacting with Polycomb proteins. Targeting Mdm2

Keywords:
EZH2Mdm2histone methylationhistone ubiquitinationpolycomb repressor complex

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DamID-seq: Genome-wide Mapping of Protein-DNA Interactions by High Throughput Sequencing of Adenine-methylated DNA Fragments
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Immunostaining for DNA Modifications: Computational Analysis of Confocal Images
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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Biology

Background:

  • Mdm2 is a key negative regulator of tumor suppressor p53.
  • Mdm2's role in cancer therapy is primarily linked to its p53-binding activity.
  • Polycomb group (PcG) proteins regulate chromatin structure and gene expression.

Purpose of the Study:

  • To investigate the p53-independent functions of Mdm2.
  • To explore Mdm2's interaction with PcG proteins and its role in gene repression.
  • To assess the implications of Mdm2's novel functions for cancer drug design.

Main Methods:

  • Investigated Mdm2's interaction with PcG proteins (PRC1 and PRC2).
  • Analyzed Mdm2's effect on gene expression profiles and chromatin modifications (H3K27me3, H2AK119ub1).
  • Assessed Mdm2's role in stem cell properties and tumor cell survival.

Main Results:

  • Mdm2 regulates gene expression similarly to PRC2, independent of p53.
  • Mdm2 promotes stemness in pluripotent and mesenchymal stem cells.
  • Mdm2 is recruited by EZH2 and enhances PRC-dependent repressive chromatin marks.
  • Mdm2 cooperates with RING1B in gene repression.

Conclusions:

  • Mdm2 possesses significant p53-independent functions in chromatin dynamics and stem cell phenotypes.
  • These novel functions of Mdm2 have critical implications for cancer drug design.
  • Current Mdm2 inhibitors targeting p53 binding may not affect these oncogenic activities.
  • Targeting Mdm2's E3 ligase activity could offer a broader therapeutic approach.