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Histone Modification02:32

Histone Modification

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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...
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Histone Modification02:32

Histone Modification

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Histone Variants at the Centromere02:30

Histone Variants at the Centromere

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Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
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Epigenetic Regulation01:46

Epigenetic Regulation

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Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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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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Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
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Related Experiment Video

Updated: Jan 31, 2026

Application of MassSQUIRM for Quantitative Measurements of Lysine Demethylase Activity
07:02

Application of MassSQUIRM for Quantitative Measurements of Lysine Demethylase Activity

Published on: March 11, 2012

13.8K

Histone demethylases regulate adipocyte thermogenesis.

Takeshi Inagaki1

  • 1Laboratory of Epigenetics and Metabolism, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8512 Japan.

Diabetology International
|January 4, 2019
PubMed
Summary

Histone demethylase JMJD1A is crucial for beige adipocyte development and energy metabolism. Its phosphorylation enables thermogenesis, offering a therapeutic target for obesity and related diseases.

Keywords:
BATBeige adiopocyteEpigeneticsHistone methylationJMJD1APPARγ

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Area of Science:

  • Cell Biology
  • Epigenetics
  • Metabolic Regulation

Background:

  • Adipocytes regulate energy metabolism; white adipocytes store energy, while brown and beige adipocytes dissipate energy through heat production.
  • Beige adipocyte formation in white adipose tissue during cold exposure involves epigenetic modifications.
  • Histone methylation is a stable epigenetic mechanism for cellular memory, with several enzymes implicated in beige adipocyte determination.

Purpose of the Study:

  • To investigate the role of histone demethylase JMJD1A in thermogenesis and beige adipogenesis.
  • To elucidate the mechanism by which JMJD1A regulates cold-induced adipocyte adaptation.
  • To assess JMJD1A as a potential therapeutic target for metabolic disorders.

Main Methods:

  • Analysis of JMJD1A phosphorylation in response to cold and beta-adrenergic stimulation.
  • Investigation of protein complex formation involving JMJD1A, SWI/SNF, PPARγ, PRDM16, and PGC1α.
  • Phenotypic analysis of Jmjd1a-null and S265A mutant mice.

Main Results:

  • JMJD1A senses cold via S265 phosphorylation, regulating acute and chronic thermogenesis.
  • Phosphorylated JMJD1A forms distinct complexes to induce gene expression in brown and beige adipocytes.
  • JMJD1A demethylates histone H3K9me2, promoting stable beige-selective gene expression.
  • Jmjd1a-null and mutant mice exhibit impaired thermogenesis and adipogenesis.

Conclusions:

  • JMJD1A is a key regulator of cold-induced thermogenesis and beige adipogenesis.
  • JMJD1A's mechanism involves recruitment to target genes and histone demethylation.
  • JMJD1A represents a promising therapeutic target for obesity, metabolic syndrome, and type 2 diabetes.