Kenneth Zaret
University of Pennsylvania, PA·Genetics
Every cell in the body carries the same DNA, yet a liver cell stays a liver cell. Part of the answer lies in how DNA is packaged.
- Fields
Genetics
Biology
Biochemistry
- Topics
chromatin
pioneer transcription factors
H3K9me3
- Grants
- 2 known grants, through Feb 2029
What they work on
- Determine how heterochromatin changes and the movement and clustering of transcription factors guide endoderm cells to become liver, using light-sheet imaging of live mouse embryos with genetic perturbations.
- Compare the periportal, midlobular and pericentral zones of the adult liver to learn how heterochromatin and protein kinetics shape normal function and repair after damage, using wild-type and heterochromatin-mutant liver slices.
- Classify pioneer transcription factors by the heterochromatin subtypes (marked by H3K9me3 or H3K27me3) they can bind, using reconstituted nucleosome arrays and pulldowns with fractionated heterochromatin.
- Map the protein domains that let pioneer factors open heterochromatin, and test whether moving these domains onto other proteins improves cell reprogramming in mice and cultured cells.
- Use dual-degron protein removal and knockdowns to learn how H3K9me3 heterochromatin is built and can be taken apart selectively, and why reprogramming factors briefly disrupt heterochromatin across the genome.
More about the research
Some regions are wrapped tightly into heterochromatin, a compact form that keeps genes switched off. To change a cell's identity, proteins called transcription factors must reach genes hidden in this packaging. The research asks how certain factors get past these barriers, and how the barriers shape liver development, upkeep and repair. The answers could help scientists make new cell types for therapy and disease modeling.
Why it matters
Understanding how cells unlock silent genes could make it more efficient to turn stem cells or mature cells into liver cells and other cell types for therapy and disease modeling. Because the same processes guide normal development and regeneration, and go wrong in pediatric diseases and adult cancers, the work may also point to ways of counteracting these conditions. It could also clarify how adult liver function might be adjusted by changing chromatin states.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Motoki Takaku
University of North Dakota, ND·Genetics
Identify the nucleosome positions and shapes that let the pioneer factor GATA3 open chromatin and drive the mesenchymal-to-epithelial transition in triple-negative breast cancer cells, using high-resolution nucleosome mapping.
Michael Joseph Buck
University at Buffalo, NY·Genetics
Determine how transcription factors recognize binding sites wrapped on a nucleosome, the DNA spool unit, using the in vitro Pioneer-seq assay to compare sites at every nucleosome position and across sequence variants.
Laura Banaszynski
University of Texas Southwestern Medical Center, TX·Genetics
Determine how phosphorylation of the histone variant H3.3 at its unique serine stimulates p300, an enzyme that acetylates histones, to produce the enhancer mark H3K27ac in mouse embryonic stem cells.
The school
University of Pennsylvania: 90 labs on PI Pages, $2.2B a year on research, 750 research doctorates a year.
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