Spatial Regulation of Histone Acetylation and Gene Expression in Drosophila Wing Disc Epithelium

Kernekoncepter

Histone acetylation patterns in the Drosophila wing disc epithelium are spatially regulated by nuclear positioning and local acetyl-CoA production from fatty acid β-oxidation, which impacts gene expression during tissue development.

Resumé

The content describes the spatial regulation of histone acetylation and gene expression in the epithelial tissue of the Drosophila wing disc. Key insights include:

Histone acetylation marks H3K18ac, H4K8ac, and total lysine acetylation are increased in the outer rim of the wing disc.
This acetylation pattern is controlled by the nuclear position within the epithelium, with nuclei exhibiting high H3K18ac levels when located closer to the tissue surface.
The surface nuclei have increased levels of acetyl-CoA synthase, which generates the acetyl-CoA required for histone acetylation.
The carbon source for histone acetylation in the rim is fatty acid β-oxidation, which is also elevated in the rim region.
Inhibition of fatty acid β-oxidation leads to decreased H3K18ac levels near genes involved in disc development, indicating the importance of this metabolic pathway in regulating chromatin state and gene expression.
The spatial acetylation pattern serves as a physical mark of the outer rim of the wing disc and other imaginal epithelia in Drosophila, affecting gene expression during tissue development.

Statistik

Histone acetylation marks H3K18ac, H4K8ac, and total lysine acetylation are increased in the outer rim of the Drosophila wing disc epithelium.
Nuclei located closer to the tissue surface exhibit higher levels of H3K18ac.
Surface nuclei have increased levels of acetyl-CoA synthase.
Fatty acid β-oxidation is elevated in the rim region of the wing disc.
Inhibition of fatty acid β-oxidation decreases H3K18ac levels near genes involved in disc development.

Citater

"Histone acetylation regulates gene expression, cell function and cell fate."
"There is a physical mark of the outer rim of the wing and other imaginal epithelia in Drosophila that affects gene expression."

Vigtigste indsigter udtrukket fra

Nuclear position and local acetyl-CoA production regulate chromatin state - Nature

by Philipp Will... kl. www.nature.com 06-05-2024

https://www.nature.com/articles/s41586-024-07471-4

Dybere Forespørgsler

How do the spatial patterns of histone acetylation and acetyl-CoA production relate to the patterning and differentiation of the wing disc during development?

The spatial patterns of histone acetylation and acetyl-CoA production play crucial roles in the patterning and differentiation of the wing disc during development. In the epithelial tissue of the Drosophila wing disc, the outer rim exhibits increased levels of histone acetylation, particularly H3K18ac and H4K8ac. This acetylation pattern is linked to the nuclear position within the epithelium, with nuclei closer to the tissue surface showing higher levels of histone acetylation. These surface nuclei also have elevated levels of acetyl-CoA synthase, which is responsible for generating the acetyl-CoA required for histone acetylation. The carbon source for histone acetylation in the outer rim is fatty acid β-oxidation, which is also upregulated in this region. Inhibition of fatty acid β-oxidation leads to decreased levels of H3K18ac near genes involved in disc development. Therefore, the spatial regulation of histone acetylation and acetyl-CoA production in the wing disc epithelium influences gene expression patterns that are essential for proper patterning and differentiation during development.

What other metabolic pathways or signaling mechanisms might contribute to the regulation of chromatin state and gene expression in the wing disc epithelium?

In addition to fatty acid β-oxidation, several other metabolic pathways and signaling mechanisms may contribute to the regulation of chromatin state and gene expression in the wing disc epithelium. One such pathway is the tricarboxylic acid (TCA) cycle, which generates metabolites that can serve as cofactors for chromatin-modifying enzymes. Metabolites like α-ketoglutarate and succinate act as substrates for histone demethylases and influence histone methylation levels. Moreover, the pentose phosphate pathway produces nucleotide precursors essential for DNA synthesis and repair, impacting gene expression through chromatin dynamics. Signaling pathways such as the mTOR pathway, which senses nutrient availability, can also modulate chromatin modifications and gene expression in response to metabolic cues. Additionally, reactive oxygen species (ROS) generated during metabolism can influence chromatin structure and gene expression by affecting the activity of histone-modifying enzymes. Therefore, a network of metabolic pathways and signaling mechanisms collaborates to regulate chromatin state and gene expression in the wing disc epithelium.

Could the principles of spatial chromatin regulation observed in the Drosophila wing disc be applicable to the development and homeostasis of other epithelial tissues in different organisms?

The principles of spatial chromatin regulation observed in the Drosophila wing disc hold significant potential for being applicable to the development and homeostasis of other epithelial tissues in different organisms. The concept of nuclear position influencing histone acetylation levels and gene expression patterns could be a conserved mechanism across various epithelial tissues. For instance, in mammalian systems, epithelial tissues undergo similar processes of differentiation and patterning during development, where spatial regulation of chromatin modifications could play a crucial role. The reliance on metabolic pathways such as fatty acid β-oxidation for histone acetylation may also be a common feature in epithelial tissues of diverse organisms. By understanding how spatial cues and metabolic signaling impact chromatin state and gene expression in the Drosophila wing disc, researchers can potentially uncover similar regulatory mechanisms in other epithelial tissues, contributing to a broader understanding of tissue development and homeostasis.