Evgeny Kvon, Ph.D.

Specific non-coding regulatory DNA elements called enhancers regulate gene transcription during animal development. The Kvon lab investigates transcriptional regulation by enhancers using cutting-edge genomics, genome editing, and transgenic tools. We are particularly interested in studying the role of enhancers in development and evolution and how enhancer malfunction leads to congenital disease.

I. Transcriptional regulation in development

The regulation of transcription plays a crucial role in animal development. It is orchestrated by enhancers, non-coding DNA elements that are bound by multiple transcription factors in a sequence-specific manner. A typical enhancer activates the expression of its target gene, often over long genomic distances, which in turn specifies the fate of different cell types during development. We are using mouse embryo development as a model system and a combination of powerful genome editing (Kvon et al., 2016) and genomics tools to understand how enhancers work in the 3D genome in the context of mammalian development.

II. Transcriptional regulation in congenital disorders

Many non-coding variants associated with congenital disorders are hypothesized to affect developmental enhancers. Determining which of these potentially pathogenic enhancer variants are important and understanding the etiology of the enhancer malfunction is a major challenge. We are using novel CRISPR/Cas9-based mouse transgenesis (Kvon et al., 2020) and cutting-edge genomics tools to understand molecular mechanisms by which pathogenic non-coding variants lead to congenital disorders.

III. Transcriptional regulation in vertebrate evolution

Changes in gene regulatory networks are hypothesized to be a primary driver of changes in body shape between different animals, but identifying genomic loci associated with major morphological transitions in vertebrates has remained challenging. The mouse is a powerful model for studying evolution loci because regulatory DNA sequences from different vertebrate species can be introduced into the mouse genome, and their activities can be directly compared with each other (Kvon et al., 2016). We are interested in using mice to further develop novel genome manipulation tools to better understand the molecular basis of vertebrate evolution.

Selected Publications

1. Chen Z, Snetkova V, Bower G, Jacinto S, Clock B, Dizehchi A, Barozzi I, Mannion BJ, Alcaina-Caro A, Lopez-Rios J, Dickel DE, Visel A, Pennacchio LA, Kvon EZ†. (2024) Increased enhancer–promoter interactions during developmental enhancer activation in mammals. Nature Genetics, Mar 20;1–11.

2. Kvon, E.Z.*†, Waymack, R., Elabd, M.G., Wunderlich, Z.*† (2021) Enhancer redundancy in development and disease. Nature Reviews Genetics, 53:521–8. PMID: 33782603

3. Kvon, E.Z., Zhu, Y., Novak, C.S., …21 authors…, Visel A., Dickel, D.E., Pennacchio, L.A. (2020) Comprehensive in vivo interrogation reveals phenotypic impact of human enhancer variants. Cell, 180(6):1262–1271. PMID: 32169219

4. Kvon, E.Z., Kamneva, O., Melo, U.S., …12 authors…, Rubin, E.M., Dickel, D.E., Pennacchio, L.A., Visel A. (2016). Progressive loss of function in a limb enhancer during snake evolution. Cell, 167(3):633-642. PMID: 27768887

5. Kvon, E.Z†. (2015). Using transgenic reporter assays to functionally characterize enhancers in animals. Genomics, 106(3):185-92. PMID: 26072435

6. Kvon, E.Z., Kazmar, T., Stampfel, G., Yáñez-Cuna, J.O., Pagani M., Schernhuber K., Dickson, B.J., Stark, A. (2014). Genome-scale functional characterization of Drosophila developmental enhancers in vivo. Nature, 512(7512):91-5. PMID: 24896182

7. Yáñez-Cuna, J.O.*, Kvon, E.Z.*, Stark, A. (2013). Deciphering the transcriptional cis-regulatory code. Trends in Genetics, 29(1):11-22. PMID: 23102583

8. Kvon, E.Z.*, Stampfel, G.*, Yáñez-Cuna, J.O., Dickson, B.J., Stark, A. (2012). HOT regions function as patterned developmental enhancers and have a distinct cis-regulatory signature. Genes & Development, 26(9):908-13. PMID: 22499593

* equal contribution. † corresponding author. For the full list of publications, please see PubMed