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Updated: Aug 6, 2026
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An Acetyl-Click Chemistry Assay to Measure Histone Acetyltransferase 1 Acetylation
Published on: January 26, 2024
Histone Acetyltransferase HAT1 Regulates Intestinal Stem Cell Proliferation and Differentiation
Prabakaran Nagarajan1, Caden J Martin1, Andrea R Keller2
1Department of Biological Chemistry and Pharmacology, Columbus, OH 43210, USA.
The Journal of Biological Chemistry
|July 24, 2026
Summary
Histone acetyltransferase HAT1 is crucial for intestinal stem cell (ISC) renewal and differentiation. Its loss disrupts ISC function, leading to altered tissue integrity and cell populations.
Area of Science:
- Cell Biology
- Genetics
- Gastroenterology
Background:
- Intestinal stem cells (ISCs) are vital for maintaining the intestinal lining.
- HAT1 (histone acetyltransferase 1) is expressed in intestinal stem and progenitor cells.
Purpose of the Study:
- To investigate the role of HAT1 in intestinal stem cell function and regulation.
- To understand the molecular mechanisms by which HAT1 influences ISC renewal and differentiation.
Main Methods:
- Inducible deletion of the HAT1 gene in intestinal epithelial cells.
- Analysis of intestinal crypt morphology, cell proliferation, and differentiation markers (OLFM+, Goblet, Paneth cells).
- Genome-wide analysis of H4K5ac and H3K9me3 modifications.
- Intestinal organoid culture to assess HAT1's role in stem cell maintenance and differentiation.
Main Results:
- Loss of HAT1 caused intestinal crypt elongation, increased stem/progenitor cell proliferation, and altered cell populations (OLFM+, Goblet cells).
- HAT1 deficiency led to mislocalization of Paneth cells and impaired differentiation in organoids.
- HAT1 specifically regulates H4K5ac in ISCs, impacting lamina-associated domains and H3K9me3 levels, thereby influencing genome-wide histone modification patterns.
Conclusions:
- HAT1 is essential for the proper renewal and differentiation of intestinal stem cells.
- HAT1 plays a critical role in maintaining intestinal stem cell function and tissue homeostasis through epigenetic regulation.
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