Jumin Zhou
Assistant Professor, The Wistar Institute

Genetics and Gene Regulation Program

Address

The Wistar Institute
3601 Spruce Street, Rm 358 (Lab)
Philadelphia, PA 19104-9999

Office tel.: 215 898-3988
Lab tel.: 215 898-3994
Fax: 215 898-0663
E-mail: zhouj@wistar.org

Link(s)

Dr Zhou at The Wistar Institute

EDUCATION

Fudan University, BS(Biology/physiology) 1982-1986.

University of Texas, MD Anderson Cancer Center, Ph.D. (biochemistry) 1990-1995.

RESEARCH INTERESTS

• Mechanism of epigenetic inheritance, long-range transcription activation, insulator and anti-insulators.

Key words:  Epignetic inheritance, insulator, anti-insulator, PTS, Drosophila, Abdominal-B, BX-C.

Search PubMed for articles

DESCRIPTION OF RESEARCH

Controlling long-range gene activations: insulators and anti-insulators

The Zhou laboratory is interested in the mechanisms that control how genes are turned on and off, using the fruit fly as an experimental model. This special class of genes, the homeotic genes, control the body plan of the entire animal kingdom. Homeotic genes turn on transcription of groups of genes to make structures such as legs, wings, and antennae develop properly. Mutations in these genes and their regulatory regions often result in developmental defects, cancer, and other diseases. Proper regulation of homeotic genes requires specialized DNA elements. The Zhou research team is specifically interested in regions of DNA that either facilitate or disrupt gene transcription. From fruit flies to humans, large gene clusters or single gene loci with complex regulatory regions are necessary to orchestrate the intricate expression patterns of proteins during developmental and physiological processes. The right protein has to be expressed at the right time. The Hox gene cluster and the beta-globin locus are excellent examples.

A central question for genes with a large and complex regulatory region is how to establish specific enhancer-promoter interactions (that is, how genes are turned on to produce a tissue-specific protein) whereby enhancer-interacting activator proteins recognize and activate specific, but often distantly located, gene promoters, and how to prevent inappropriate interactions, and thereby mistakes in development. A class of special DNA regions called insulators, or chromatin boundary elements, have been identified from yeast to man. These elements are believed to organize genomes into distinct areas called functional loop domains to restrict regulatory activity locally, thus preventing inappropriate mis-regulations.

Insulators are believed to exist between neighboring genes to prevent enhancers from activating the wrong promoters. However, Dr. Zhou and others have identified several insulator-like DNA elements from the regulatory region of homeotic gene Abdominal-B. In collaboration with others, they have identified a protein dCTCF, the Drosophila orthologue of the vertebrate insulator protein CTCF, which functions through one of these elements, Fab-8. These studies support the model proposed by the Karch’s and Schedl’s groups that the Abdominal-B regulatory region is organized by insulators into several tissue specific loop domains.

The presence of insulator obviously will pose a problem for enhancers that are destined to activate Abdominal-B: how do they communicate with the promoter over the insulator elements. A few years ago Dr. Zhou identified a novel regulatory element from one of the loop domains called the Promoter Targeting Sequence (PTS) that has an anti-insulator activity. This permits an enhancer to activate a promoter despite an intervening insulator. Recent work from this group found the PTS also possesses a "promoter targeting" function, whereby restricting the enhancer activity to a single promoter even when more than one promoter is available. They also showed that the PTS facilitates the activity of a distant enhancer. These studies clearly suggest that the PTS may normally mediate enhancer-promoter communications in the Abdominal-B locus by overcoming the insulator elements such as Fab-8. Consequently, the insulator elements, such as Fab-7 and Fab-8 are converted into local chromatin boundary elements, which confine differential chromatin structure within each domain. The Zhou lab is now engaged in determining the basic biological properties of PTS and identifying the genes and proteins that mediate its activity.

RECENT PUBLICATIONS

Chen, Q., Lin, Q., Lin, L., Smith, S., and Zhou, J. (2005). Multiple PTS elements from the Abdominal-B locus mediate long-range enhancer-promoter communications. Developmental Biology. In press.

Zhou, J., Berger, S.L. (2004). Good fences make good neighbors: barrier elements and genomic regulation. Mol Cell 16:500-502.

Lin, Q., Chen, Q., Lin, L., Zhou, J. (2004). The Promoter Targeting Sequence mediates epigenetically heritable transcription memory. Genes Dev 18:2639-2651.

Lin, Q., Di Wu., and Zhou, J. (2003). The PTS element facilitates and restricts a distant enhancer to a single promoter in the transgenic Drosophila embryos. Development. 130, 519-526.

Zhou, J., and Levine, M. (1999). A novel cis-regulatory element, the PTS, mediates an anti-insulator activity in the Drosophila embryo. Cell. 99, 567-575.

Lab

ROTATION PROJECTS FOR 2005-2006

1. Characterizing proteins interacting with the PTS.
2. Genetic analysis of genes involved in PTS function.
3. Identification of additional DNA/protein components of the Fab-8 insulator.
4. Genetic analysis of genes important for dCTCF insulator function.

Lab personnel:

Qi Chen, PhD - Postdoctoral Fellow
Sheryl Smith, PhD - Postdoctoral Fellow
Yanping Du, Ph.D. – Postdoctoral Fellow
Lan Lin, M.S. – Research Assistant III
Ian Thomas, B.S. – Research Assistant I
Joy Deng – Undergraduate Student