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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, a histone acetyltransferase, is expressed in ISCs 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.
- Genome-wide characterization of HAT1-dependent histone modifications (H4K5ac, H3K9me3).
- Intestinal organoid culture to assess HAT1 function in vitro.
Main Results:
- Loss of HAT1 elongated intestinal crypts, increased ISC proliferation, and altered cell differentiation (more Goblet cells, mislocalized Paneth cells).
- HAT1 specifically acetylates H4K5ac in ISCs, primarily in lamina-associated domains.
- HAT1 deficiency led to increased H3K9 tri-methylation, indicating altered genome-wide histone modification patterns.
- HAT1 is essential for ISC maintenance (Lgr5+ cells) and differentiation in organoid models.
Conclusions:
- HAT1 is indispensable for the proper regulation of intestinal stem cell renewal and differentiation.
- HAT1-mediated H4K5ac plays a key role in maintaining intestinal stem cell function and genome stability.
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