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Related Concept Videos

Transcription Factors02:16

Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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RNA Polymerase II Accessory Proteins02:36

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Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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Co-activators and Co-repressors02:04

Co-activators and Co-repressors

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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...
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Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

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Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
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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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General Transcription Factors01:30

General Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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A functional element necessary for fetal hemoglobin silencing.

Vijay G Sankaran1, Jian Xu, Rachel Byron

  • 1Department of Medicine, Children's Hospital Boston, Boston, MA 02115, USA. sankaran@broadinstitute.org

The New England Journal of Medicine
|September 2, 2011
PubMed
Summary
This summary is machine-generated.

Researchers identified a key 3.5-kb intergenic region near the delta-globin gene essential for silencing fetal hemoglobin (HbF) in adults. This finding advances understanding of HbF regulation and potential therapies for beta-hemoglobinopathies.

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Area of Science:

  • Genetics and Molecular Biology
  • Hematology
  • Gene Regulation

Background:

  • Understanding fetal hemoglobin (HbF) gene regulation is crucial for developing therapies for beta-hemoglobinopathies.
  • While trans-acting factors are known, cis-regulatory elements controlling HbF remain largely uncharacterized.

Purpose of the Study:

  • To identify cis-regulatory elements involved in fetal hemoglobin gene silencing.
  • To elucidate the genetic basis of unusual hemoglobin expression patterns in specific families.

Main Methods:

  • Array comparative genomic hybridization (aCGH) to map deletions in the beta-globin locus.
  • Polymerase-chain-reaction (PCR) assays and DNA sequencing to confirm breakpoints.
  • Chromatin immunoprecipitation (ChIP) to study trans-acting factor binding.

Main Results:

  • Identified a novel (δβ)(0)-thalassemia deletion and a hereditary persistence of fetal hemoglobin deletion.
  • Discovered a 3.5-kb intergenic region near the 5' end of the delta-globin gene essential for gamma-globin (fetal hemoglobin) silencing.
  • Confirmed that BCL11A, a key HbF silencing factor, binds to this intergenic region in adult erythroid cells.

Conclusions:

  • An intergenic region near the delta-globin gene is critical for fetal hemoglobin silencing.
  • This discovery provides a new target for therapeutic strategies aimed at inducing fetal hemoglobin.
  • Findings advance the understanding of beta-globin locus regulation and its implications for hemoglobinopathies.