Elissa Lei, Ph.D. : NIDDK

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Epifluorescent whole mount staining of third instar larval imaginal disc to visualize insulator bodies using anti-CP190 antibodies (green) and DAPI (blue).
Epifluorescent whole mount staining of third instar larval imaginal disc to visualize insulator bodies using anti-CP190 antibodies (green) and DAPI (blue).

Elissa Lei, Ph.D.

NIDDK, National Institutes of Health
Building 50, Room 3148
50 South Dr.
Bethesda, MD 20892-8028
Tel: 301-435-8989
Fax: 301-496-5239
Email: leielissa@mail.nih.gov

Research Website:

Education / Previous Training and Experience:
Elissa Lei obtained her Ph.D. in 2003 for her work on mRNA nuclear export in the laboratory of Pamela Silver at Harvard Medical School. Her postdoctoral research on RNA silencing and chromatin organization was carried out in the laboratory of Victor Corces at Johns Hopkins University. She established her independent research group in 2006 in the Laboratory of Cellular and Developmental Biology.

Research Statement:

Chromatin organization and RNA silencing in Drosophila

It has become increasingly apparent that proper control of gene expression requires complex organization of DNA at the level of chromatin. Chromatin insulators influence gene expression by establishing chromatin domains subject to distinct transcriptional controls, likely through alteration of their spatial organization. Insulators enforce the strict specific and temporal expression of complex loci such as the Drosophila Bithorax complex, a master regulator of body segmentation, and the vertebrate beta-globin locus, which changes in expression during erythroid development. In humans, disruption of the CTCF insulator protein can lead to myc oncogene overexpression and has been implicated in human breast and colorectal cancers. Therefore, studying the mechanism and regulation of insulator function is essential to further understand how higher order chromatin structure influences the intricately orchestrated transcriptional programs needed for proper development and differentiation.

The focus of our work is the gypsy chromatin insulator of Drosophila, the best studied chromatin insulator to date. The gypsy insulator is comprised of a DNA sequence bound by a complex of at least three proteins. Several lines of evidence suggest that insulator proteins bridge distant DNA sequences dispersed throughout the genome, causing looping of the DNA and the creation of a distinct chromatin domain. Nuclear aggregates of insulator complexes termed insulator bodies are tethered stably to the nuclear matrix and may form higher order structures of chromatin loops. Interestingly, insulator body association with the nuclear scaffold can be disrupted by RNase A treatment. These findings prompted us to examine whether RNA silencing, an RNA-dependent cellular mechanism of gene regulation known to act on the level of chromatin, affects gypsy insulator activity.

Our research provides evidence for a previously unknown role for RNA silencing in gypsy insulator function as well as higher order chromatin organization. Using biochemical purification techniques, we have identified an RNA-dependent physical interaction between proteins required for proper gypsy insulator and RNA silencing function. Furthermore, mutations in genes encoding RNA silencing components affect gypsy insulator activity in vivo and the formation of insulator bodies. These results suggest that RNAs involved in the RNA silencing pathway are responsible for the multimerization of insulator complexes and/or the ability of insulator bodies to interact with a nuclear scaffold. Our current efforts center on identifying RNAs associated with the gypsy insulator and gaining mechanistic insight into how the RNA silencing machinery participates in gypsy insulator function using both biochemical and genetic approaches. A second major project in our laboratory is to develop cell culture assays for insulator function and employ high throughput double-stranded RNA knockdown technologies to identify novel factors involved in insulator function and nuclear organization.

Noncoding RNAs: Silent No MoreAn eBriefing of the New York Academy of Sciences Exit Disclaimer 

Selected Publications:

Gerasimova TI, Lei EP, Bushey AM, Corces VG Coordinated Control of dCTCF and gypsy Chromatin Insulators in Drosophila. Mol Cell (28): 761-72, 2007. [Full Text/Abstract]

Caretti G, Lei EP, Sartorelli V The DEAD-Box p68/p72 Proteins and the Noncoding RNA Steroid Receptor Activator SRA: Eclectic Regulators of Disparate Biological Functions. Cell Cycle (6), 2007. [Full Text/Abstract]

Lei EP, Corces VG  A long-distance relationship between RNAi and Polycomb.  Cell (124): 886-8, 2006. [Full Text/Abstract]

Lei EP, Corces VG  RNA interference machinery influences the nuclear organization of a chromatin insulator.  Nat Genet (38): 936-41, 2006. [Full Text/Abstract]

Pai CY, Lei EP, Ghosh D, Corces VG  The centrosomal protein CP190 is a component of the gypsy chromatin insulator.  Mol Cell (16): 737-48, 2004. [Full Text/Abstract]

Page last updated: January 13, 2009

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