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Related Concept Videos

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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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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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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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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Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

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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...
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Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Acss2 Deletion Reveals Functional Versatility via Tissue-Specific Roles in Transcriptional Regulation.

Narayanan Puthillathu Vasudevan1, Dharmendra K Soni1, John R Moffett1

  • 1Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

International Journal of Molecular Sciences
|February 25, 2023
PubMed
Summary

The acetate activating enzyme, acyl-coenzyme A synthetase short-chain family member 2 (Acss2), regulates cellular processes. Loss of Acss2 causes organ-specific changes in gene expression, not fatty acid composition.

Keywords:
ATP citrate lyaseacetateacetyl-CoA synthetaseacetyl-coenzyme Aacetylationtranscriptional regulation

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Area of Science:

  • Metabolic regulation
  • Molecular biology
  • Systems physiology

Background:

  • Cellular processes are coordinated by metabolic enzymes that adapt metabolism to physiological conditions.
  • Acyl-coenzyme A synthetase short-chain family member 2 (Acss2) is an acetate-activating enzyme primarily known for its lipogenic role.
  • Emerging evidence indicates Acss2 possesses regulatory functions beyond acetyl-CoA provision for lipid synthesis.

Purpose of the Study:

  • To investigate the regulatory roles of Acss2 in distinct organ systems.
  • To examine transcriptomic alterations and fatty acid constitution changes in Acss2 knockout mice (Acss2-/-) in the liver, brain, and adipose tissue.

Main Methods:

  • Utilized Acss2 knockout mouse models.
  • Performed transcriptomic analysis to identify changes in gene expression.
  • Assessed fatty acid composition in key metabolic tissues.

Main Results:

  • Acss2 deletion resulted in organ-specific dysregulation of signaling pathways, transcriptional regulators, cellular processes, and biological functions in the liver, brain, and mesenteric adipose tissue.
  • Transcriptional changes were distinct across the three organ systems, reflecting their unique physiological roles.
  • Despite significant transcriptomic alterations, the loss of Acss2 led to minimal changes in fatty acid constitution in all examined tissues.

Conclusions:

  • Acss2 loss induces distinct organ-specific transcriptional regulatory patterns that align with the complementary functions of the liver, brain, and adipose tissue.
  • Acss2 acts as a transcriptional regulatory enzyme, influencing key transcription factors and pathways under normal physiological conditions.
  • These findings confirm Acss2's broader regulatory role in cellular metabolism and gene expression.