Judith A. Kassis, Ph.D.
Section on Gene Expression
During development and differentiation, genes either become competent to be expressed or are stably silenced in an epigenetically heritable manner. This selective activation/repression of genes leads to the differentiation of tissue types. Recent evidence suggests that modifications of histones in chromatin contribute substantially to determining whether a gene will be expressed. Our group is interested in understanding how chromatin-modifying protein complexes are recruited to DNA. In Drosophila, two groups of genes, the Polycomb group (PcG) and Trithorax group (TrxG), are important for inheritance of the silenced and active chromatin state, respectively. Regulatory elements called Polycomb group response elements (PRE) are cis-acting sequences required for the recruitment of chromatin-modifying PcG protein complexes. TrxG proteins may act through either the same or overlapping cis-acting sequences. Our group aims to understand how PcG and TrxG proteins are recruited to DNA. We are also interested in how distantly located transcriptional enhancer elements are able to selectively activate a promoter that may be tens (or even hundreds) of kilobases away. Our data suggest that promoter-proximal elements, some of which overlap with PREs, impart specificity to promoter-enhancer communication. Finally, we are interested in the coordination between activation by enhancer elements and silencing by PcG proteins. Our data suggest that certain types of transcriptional activators may be able to overcome the repressive activity of PcG proteins, which may be particularly important at the PcG target gene engrailed, at which PcG binding is constitutive; that is, PcG proteins are present even in cells in which engrailed is actively transcribed. Finally, we study the overall chromatin architecture and also unusual regulatory DNA mutations in order to understand how intra- and inter-chromosomal interactions influence gene expression and development. These studies will lead to a better understanding of how gene expression is controlled as cell fates are determined and what "locks in" the determined state.
Dr. Judy Kassis is the head of the Section on Gene Expression, Division of Developmental Biology, NICHD. Dr. Kassis obtained her Ph.D. in 1983 at the University of Wisconsin, Madison. She did postdoctoral research at the University of California, San Francisco and then joined the Center for Biological Research and Evaluation (CBER), FDA as a tenure-track investigator in 1987. At CBER she conducted research on the control of gene expression and transposon homing using the model system Drosophila and was a product reviewer and license chair for biological products. She joined the Laboratory of Molecular Genetics, NICHD as a Senior Investigator in 1999. Dr. Kassis studies epigenetic silencing by the Polycomb group of transcriptional repressors using Drosophila as a model system. Her lab was the first to show the involvement of specific DNA binding proteins in recruitment of Polycomb repressive complexes to the DNA. She is also interested in how transcriptional enhancers, often located 50kb or more away from the promoters they regulate, achieve their specificity. She has served on the NIH, NRSA Genes and Genomic study section, the NIH, MGA study section and is a reviewer of many papers for Science, Nature Communications, PNAS, Development, Developmental Biology, Molecular and Cellular Biology, Genetics, and PLoS Genetics.
Kuroda MI, Kang H, De S, Kassis JA. Dynamic Competition of Polycomb and Trithorax in Transcriptional Programming. Annu Rev Biochem. 2020;89:235-253.
De S, Cheng Y, Sun MA, Gehred ND, Kassis JA. Structure and function of an ectopic Polycomb chromatin domain. Sci Adv. 2019;5(1):eaau9739.
Brown JL, Sun MA, Kassis JA. Global changes of H3K27me3 domains and Polycomb group protein distribution in the absence of recruiters Spps or Pho. Proc Natl Acad Sci U S A. 2018;115(8):E1839-E1848.
De S, Mitra A, Cheng Y, Pfeifer K, Kassis JA. Formation of a Polycomb-Domain in the Absence of Strong Polycomb Response Elements. PLoS Genet. 2016;12(7):e1006200.
Ray P, De S, Mitra A, Bezstarosti K, Demmers JA, Pfeifer K, Kassis JA. Combgap contributes to recruitment of Polycomb group proteins in Drosophila. Proc Natl Acad Sci U S A. 2016;113(14):3826-31.
Related Scientific Focus Areas
Genetics and Genomics
This page was last updated on September 8th, 2020