M Andrew Hoyt

Xin Chen

Assistant Professor
Department of Biology

CMDB Graduate Program Faculty


B.S.
University of Science & Technology of China (USTC), Hefei, China
Ph.D.
University of Texas at Austin, Texas

Postdoctoral
Stanford University School of Medicine, California


 

Department of Biology
Johns Hopkins University
3400 North Charles Street
Baltimore, MD 21218-2685
U.S.A.
Office Telephone:
Lab Telephone:
Department Fax:
Email:
410.516.4576
410.516.6543
410.516.5213
xchen32@jhu.edu


Office- Mudd 307B
Lab- Mudd 300 and 307A


[Research Interests] [Representative Publications] [Lab Members]


RESEARCH INTERESTS


Epigenetic regulation of Drosophila germ cell differentiation from a stem cell lineage

A broad definition for “epigenetic phenomenon” refers to effects on gene expression or function that are heritable through many cell divisions without altering the primary DNA sequences. Epigenetic regulation can act through different mechanisms, including post-translational modifications of histones and localization of the chromatin modifiers to particular subnuclear regions. Failure in appropriate epigenetic regulation may lead to abnormalities in development and may also underlie early steps in cancer genesis.

During normal development, the mechanisms that regulate differentiation of cells from undifferentiated precursors play key roles in tissue/organ development and maintenance, such as gametogenesis. Precursor germ cells must commit to differentiate at the right place and with the right timing to generate and maintain the pools of functional gametes. The maintenance of the precursor germ cells in an undifferentiated and proliferative state and the subsequent reversal of these controls to allow terminal differentiation are both critical to continuous production of gametes throughout lifetime.

The Drosophila male germ line provides a powerful model system for studying the mechanisms that regulate differentiation in adult stem cell lineages. My laboratory will utilize it as a model system to study how genetic and epigenetic mechanisms interplay to ensure proper gene expression during spermatogenesis.

The roles of PcG components in precursor cell proliferation vs. differentiation
Emerging evidence indicates that transcriptional repression by the Polycomb group (PcG) machinery may be required to maintain terminal differentiation genes at a silenced state in precursor cells, in both embryonic and adult stem cell lineages. A major question is how this epigenetically silenced state could be reversed to allow expression of differentiation genes during normal development. Our previous discoveries indicated that tissue-specific transcription regulators might counteract PcG silencing and turn on certain terminal differentiation genes. In addition, different PcG components are either differentially expressed, or localized to distinct subnuclear domains, indicating they themselves are developmentally regulated. Our future studies will address the mechanisms how PcG expression/localization is regulated and how PcG regulates germ cell development. Results from these studies may have implications on understanding differentiation of other adult stem cells as well as embryonic stem cell.

Epigenetic mechanisms that regulate the switch from transit-amplifying precursor cells to differentiating cells
Our previous work has revealed a set of stage-specific modifications of the chromatin landscape, including changes in chromatin modifying enzymes and many covalent histone modifications, accompany the key transition from proliferative precursor to differentiating germ cells. Further studies will utilize molecular, genetic and biochemical approaches to investigate: (1) What are the epigenetic signatures underlying the chromatin landscape switch from precursor to differentiating cells? (2) Which enzymes generate and recognize the specific epigenetic marks? (3) How do the alterations in the epigenetic modifications affect target gene expression and germ cell development? To date, much of the knowledge about the epigenetic regulation of gene expression comes from in vitro studies; we have a unique system to investigate the in vivo mechanisms in the context of normal development.

 


REPRESENTATIVE PUBLICATIONS


Chen, X. 2008. Stem cells- what can we learn from flies? Invited review for Fly. FLY 2-1: 19- 28.

Krishnamoorthy, T., Chen, X., Govin, J., Cheung, W.L., Dorsey, J., Schindler, K., Winter, E., Allis, C. D., Khochbin, S., Fuller, M. T., and Berger, S. L. 2006. Phosphorylation of histone H4 Ser1 regulates sporulation in yeast and is conserved in fly and mouse spermatogenesis. Genes and Development. 20: 2580–2592.

Chen, X., Hiller, M., Sancak, Y. and Fuller, M. T. 2005. Tissue specific TAFs counteract Polycomb to turn on terminal differentiation. Science. 310: 869- 872.

Hiller, M., Chen, X., Pringle, M.J., Suchorolski, M., Sancak, Y., Viswanathan, S., Bolival, B., Marino, S. and Fuller, M.T. 2004. Testis-specific TAF homologs collaborate to control a tissue-specific transcription program. Development. 131: 5297-5308.

Overstreet, E., Chen, X., Wendlend, B., and Fischer, J. A. 2003. Either part of a Drosophila Epsin protein, divided after the ENTH domain, functions in endocytosis of Delta in the developing eye. Current Biology. 13: 854-860.

Chen, X., Zhang, B. and Fischer, J. A. 2002. A specific protein substrate for deubiquitinating enzyme: Liquid facets is the substrate of Fat facets. Genes and Development. 16: 289-294. One of the cover stories.

Chen, X. and Fischer, J. A. 2002. A P element transformation vector for high levels of gene expression in germline cells of the ovary and undifferentiated cells in the developing eye of Drosophila. Plasmid. 47: 61- 65.

Chen, X. and Fischer, J. A. 2000. In vivo structure/function analysis of the Drosophila fat facets deubiquitinating enzyme gene. Genetics. 156: 1829-1836

Chen, X.*, Li, Q.* and Fischer, J. A. 2000. Genetic analysis of the Drosophila DNAprim gene: The function of the 60-kD primase subunit of DNA polymerase opposes the fat facets signaling pathway in the developing eye. Genetics 156: 787-1795. (* indicating authors of equal contribution.)

Chen, X., Overstreet, E., Wood, S. A. and Fischer, J. A. 2000. On the conservation of function of the Drosophila Fat facets deubiquitinating enzyme and Fam, its mouse homolog. Dev. Genes Evol. 210: 603- 610.


Lab Members


 Postdoctoral Fellows:
Suk Ho Eun
Qiang Gan

Graduate Students:
Cindy Lim
Lama Tarayrah
Vuong Tran

Undergraduates:
Andrew Mo
Derek Ho
Caitlin Choi
Michele Ly
Rodrigo Gacel Arzate Mejía


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