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Zeitlinger Lab

We seek to understand how different stretches of DNA provide information for gene transcription, expression, and regulation by developing computational tools for analyzing vast quantities of genetic information.

Research Summary

How do non-coding sequences of DNA regulate genes?

Research Areas

Genetics and Genomics, Development and Regeneration, Molecular and Cell Biology, Systems Biology

Organisms

Mice, Fruit flies

The Zeitlinger Lab focuses on how DNA sequence information in the genome controls gene regulation in Drosophila and mice to gain insight that can be applied to the human genome in development and disease.

Gene regulation is the process by which a cell determines which genes to turn on and off and when to create specific cells in the body. The Zeitlinger Lab analyzes whole genomes to predict the fate of cells.

Zeitlinger discovered that paused RNA polymerase II is found genome-wide. RNA polymerase II starts the transcription process - producing RNA messages from DNA - but then pauses, as if waiting for a signal to proceed. If paused polymerase is present, the gene is more likely to be activated in the future.

The Zeitlinger Lab develops genomic techniques, including ChIP-nexus, that allow researchers to collect information from vast amounts of cells — sometimes numbering in the millions — to provide an accurate picture of how genes are regulated. They also apply deep learning to ChIP-nexus data from different cell types and stages to better understand the cis-regulatory code (how regulatory DNA sequences affect neighboring genes) and how this code changes during development. Additional technology developed is ChIP-next that allows deciphering of cis-regulatory information, stretches of non-coding DNA that regulate gene expression, from many fewer cells.

Principal Investigator

Julia Zeitlinger

Investigator

Stowers Institute for Medical Research

Get to know the lab

Zeitinger and her team developed ChIP-nexus, an innovative technique described in Nature Biotechnology in 2015, which gives investigators an accurate high-resolution map of transcription binding sites.

Dr. Julia Zeitlinger's lab team standing on a bridge above a small stream at the Stowers Institute in Kansas City

Our Team


Featured Publications

TATA and paused promoters active in differentiated tissues have distinct expression characteristics

Ramalingam V, Natarajan M, Johnston J, Zeitlinger J. Mol Syst Biol. 2021;17:e9866. doi: 10.15252/msb.20209866.

Seven myths of how transcription factors read the cis-regulatory code

Zeitlinger J. Curr Opin Syst Biol. 2020;23:22-31.

Base-resolution models of transcription-factor binding reveal soft motif syntax

Avsec Z, Weilert M, Shrikumar A, Krueger S, Alexandari A, Dalal K, Fropf R, McAnany C, Gagneur J, Kundaje A, Zeitlinger J. Nat Genet. 2021;53:354-366.

Reporter-ChIP-nexus reveals strong contribution of the Drosophila initiator sequence to RNA Polymerase pausing

Shao W, Alcantara SG, Zeitlinger J. eLife. 2019;8:e41461. doi: 41410.47554/eLife.41461.

Paused RNA polymerase II inhibits new transcriptional initiation

Shao W, Zeitlinger J. Nat Genet. 2017;49:1045-1051.

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Drosophila poised enhancers are generated during tissue patterning with the help of repression

Koenecke N, Johnston J, He Q, Meier S, Zeitlinger J. Genome Res. 2017;27:64-74.

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