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Related Concept Videos

Chromatin Immunoprecipitation- ChIP02:36

Chromatin Immunoprecipitation- ChIP

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...
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
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 Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...
Heterochromatin02:38

Heterochromatin

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...
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...

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Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
11:07

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding

Published on: September 21, 2011

Chromatin accessibility pre-determines glucocorticoid receptor binding patterns.

Sam John1, Peter J Sabo, Robert E Thurman

  • 1Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Nature Genetics
|January 25, 2011
PubMed
Summary
This summary is machine-generated.

Glucocorticoid receptor binding preferentially targets accessible chromatin, not random sites. This pre-existing accessibility dictates cell-specific factor occupancy, explaining tissue selectivity of steroid drugs.

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Area of Science:

  • Molecular Biology
  • Genomics
  • Cellular Regulation

Background:

  • Cellular development and response involve transcriptional factors binding to DNA.
  • The mechanism for selective in vivo target binding by transcriptional factors remains unclear.
  • Glucocorticoid receptor (GR) is a key ligand-activated transcription factor.

Purpose of the Study:

  • To investigate the mechanism of de novo genomic binding by the glucocorticoid receptor.
  • To determine how GR selects specific genomic targets from numerous potential sites.
  • To understand the basis of cell- and tissue-specific GR binding patterns.

Main Methods:

  • Analysis of de novo genomic binding sites for the glucocorticoid receptor.
  • Assessment of chromatin accessibility patterns in various cell types.
  • Correlation of GR binding with preexisting foci of accessible chromatin and local sequence features.

Main Results:

  • Up to 95% of de novo GR binding occurs at preexisting accessible chromatin regions.
  • GR binding enhances local chromatin accessibility.
  • Cell-specific GR occupancy is primarily determined by cell-specific baseline chromatin accessibility.

Conclusions:

  • Regulatory factor-genome interactions are guided by pre-existing chromatin accessibility.
  • This mechanism provides a framework for understanding transcriptional factor targeting.
  • Identifies a molecular basis for the tissue selectivity of steroid pharmaceuticals.