Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

6.8K
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....
6.8K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

9.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.0K
Histone Modification02:32

Histone Modification

13.1K
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...
13.1K
Histone Variants at the Centromere02:30

Histone Variants at the Centromere

4.3K
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...
4.3K
Overview of DNA Repair02:25

Overview of DNA Repair

30.4K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
30.4K
Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

8.2K
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...
8.2K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Market trading method for hydrogen production and refueling integrated station operator under hydrogen sharing mechanism.

Scientific reports·2026
Same author

Emergence of ceftazidime-avibactam resistance mediated by KPC variants KPC-71 and KPC-78 in ST463 <i>Pseudomonas aeruginosa</i>.

Microbiology spectrum·2026
Same author

Author Correction: Epitranscriptomic RNA editing resolves Mus81 DNA repair tradeoffs in heat tolerance and meiosis.

Nature communications·2026
Same author

Identification of vacuum OLTC faults using improved multimodal PKO-SVM.

Scientific reports·2026
Same author

Fructose-Induced bioenergetic surplus Unlocks fatty acid biosynthesis pathway dominance over reverse β-Oxidation: Mechanistic insights into High-Caproate production from food waste.

Bioresource technology·2026
Same author

The impact of 1-hour plasma glucose on the metabolic characteristics and pregnancy outcomes in polycystic ovary syndrome.

Nutrition & diabetes·2026

Related Experiment Video

Updated: Jun 7, 2025

Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique
09:14

Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique

Published on: January 14, 2016

9.1K

Human HDAC6 senses valine abundancy to regulate DNA damage.

Jiali Jin1, Tong Meng1,2, Yuanyuan Yu3

  • 1Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Nature
|November 20, 2024
PubMed
Summary

Histone deacetylase 6 (HDAC6) acts as a valine sensor, regulating DNA damage and demethylation in response to valine levels. Dietary valine restriction shows promise for cancer therapy.

More Related Videos

Visualization of DNA Repair Proteins Interaction by Immunofluorescence
07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

10.1K
Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
09:20

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS

Published on: August 10, 2017

8.5K

Related Experiment Videos

Last Updated: Jun 7, 2025

Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique
09:14

Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique

Published on: January 14, 2016

9.1K
Visualization of DNA Repair Proteins Interaction by Immunofluorescence
07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

10.1K
Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
09:20

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS

Published on: August 10, 2017

8.5K

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • Valine, an essential branched-chain amino acid, is crucial for protein synthesis, neurological function, and hematopoiesis.
  • The cellular mechanisms for sensing valine abundance and its downstream effects remain largely unknown.
  • Understanding valine sensing is critical for elucidating its role in physiological processes and diseases like leukemia.

Purpose of the Study:

  • To identify the molecular sensor responsible for detecting intracellular valine levels.
  • To elucidate the mechanism by which valine sensing influences cellular functions, particularly DNA integrity.
  • To explore the therapeutic potential of manipulating valine levels in cancer treatment.

Main Methods:

  • Biochemical assays to demonstrate direct binding of valine to HDAC6.
  • Cellular fractionation and imaging to track HDAC6 localization under varying valine conditions.
  • DNA damage assays and analysis of DNA demethylation markers (TET2, TDG).
  • In vivo studies using xenograft and patient-derived xenograft models with dietary valine restriction.

Main Results:

  • Human histone deacetylase 6 (HDAC6) directly binds valine via a primate-specific domain, functioning as a valine sensor.
  • Intracellular valine levels control the nuclear-cytoplasmic shuttling of human HDAC6.
  • Valine deprivation causes nuclear retention of HDAC6, leading to TET2 deacetylation, active DNA demethylation, and subsequent DNA damage.
  • Dietary valine restriction suppressed tumor growth in preclinical models and improved PARP inhibitor efficacy.

Conclusions:

  • Human HDAC6 serves as a critical sensor for intracellular valine, linking nutrient status to DNA integrity.
  • HDAC6-mediated regulation of DNA demethylation and damage in response to valine deprivation is a novel biological pathway.
  • Dietary valine restriction represents a promising strategy for cancer therapy, potentially enhancing existing treatments like PARP inhibitors.