Rupa Sridharan
University of Wisconsin-Madison, WI·Genetics
Every cell in the body carries the same DNA, yet cells become very different from one another. Part of the answer lies in chemical tags on DNA and on the histone proteins that package it, which switch genes on or off without changing the underlying sequence.
- Fields
Genetics
Biochemistry
Biology
- Topics
epigenetics
histone demethylase
H3K9me2
- Grants
- 1 known grant, through Mar 2027
What they work on
- Test how KDM3B, an enzyme that removes the repressive H3K9me2 histone mark, controls DNA demethylation carried out by the Tet enzymes during the transition from the post-implantation epiblast to primordial germ cells.
- Determine how the interaction between KDM3B and PRMT5, the methyltransferase that places arginine methylation on histones H2A and H4, coordinates the exchange of repressive marks for new ones in germ cell precursors.
- Define the post-transcriptional role of KDM3A and KDM3B, examining their interaction with mRNA processing machinery and how this shapes gene expression during early development.
- Establish the temporal order and interdependence of global epigenetic changes in primordial germ cell specification, including loss of H3K9me2 and DNA methylation at repetitive elements.
More about the research
One of the most dramatic resets of these tags happens in primordial germ cells, the small group of cells that leave the early embryo, travel to the developing gonad, and become the precursors of eggs and sperm. This project asks how that reset is timed and coordinated, because erasing the tags incompletely or in the wrong places can cause imprinting defects and can pass altered states to the next generation.
Why it matters
How the epigenetic marks on DNA are erased and rewritten in the cells that become eggs and sperm determines whether genomic imprints are set correctly and whether altered states are inherited by the next generation. Clarifying the role of the KDM3 family of histone demethylases in this process adds to understanding of early developmental disorders and infertility, and could eventually inform how such conditions are diagnosed or explained.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Songtao Jia
Columbia University, NY·Genetics
Determine how ubiquitylation of histone H3 at lysine 14 (H3K14ub) stimulates the H3K9 methyltransferase enzymes that create heterochromatin's key silencing mark in fission yeast.
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.
Robert Schmitz
University of Georgia, GA·Genetics
Map accessible chromatin at single-cell resolution across multiple maize genetic backgrounds to identify cell-type-specific regulatory regions and transcription factor binding events.
The school
University of Wisconsin-Madison: 91 labs on PI Pages, $1.9B a year on research, 854 research doctorates a year.
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