Ken-ichi Noma, Ph.D.

Assistant Professor
Gene Expression and Regulation Program
215-898-3933, Office

Introduction

The laboratory of Ken-ichi Noma, Ph.D., focuses on the mechanisms that regulate three-dimensional higher-order genome structure, influencing various biological processes.  Defective organization of higher-order genome structure is known to be involved in human diseases, including many cancers.  By uncovering the molecular mechanisms governing higher-order genome structure and its biological significance, the laboratory aims to establish a mechanistic framework for understanding the molecular etiology for human diseases related to nuclear organization.

Research Summary

The eukaryotic genome is extensively but precisely folded in the nucleus. For instance, the human genome is composed of ~ 1.8 m of DNA fiber packaged into a ~ 6 µm diameter nuclear compartment. Such genome packaging is not only brought about by condensing genetic material, but spatial positioning of distinct chromosomal loci, referred to higher-order genome organization, and also has critical roles in various DNA regulatory activities such as transcription and DNA replication.

We have recently discovered that the evolutionarily conserved TFIIIC complex, a well-known transcription factor for RNA polymerase III transcribing small non-coding RNAs including tRNAs, participates in organizing higher-order genome structure in fission yeast. We have also shown that TFIIIC binding to specific DNA sequences is critical for boundary function demarcating chromosomal domains. Our laboratory is currently seeking to better understand the TFIIIC-dependent three-dimensional organization of the genome. We are also exploring a number of other currently uncharacterized mechanisms governing higher-order genome structure.

The overall goal of our laboratory is to determine the in vivo three-dimensional genome structure and to elucidate its influence on DNA regulatory activities. In order to achieve this goal, our group employs genomic assays, fluorescent microscopy, molecular biology, and biochemical approaches, in addition to exploiting the power of yeast genetics. Ultimately, we will extend our research regarding nuclear organization in fission yeast into mammalian systems to characterize the molecular pathology of human diseases, including cancers.

Selected Publications

Noma K, Cam HP, Maraia RJ, Grewal SIS. A role for TFIIIC transcription factor complex in genome organization. Cell 125, 859-872, 2006

Noma K, Sugiyama T, Cam H, Verdel A, Jia S, Zofall M, Jia S, Moazed D, Grewal SIS. RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing. Nature Genetics 36, 1174-1180, 2004

Noma K, Grewal SIS. Histone H3 lysine 4 methylation is mediated by Set1 and promotes maintenance of active chromatin states in fission yeast. Proc. Natl. Acad. Sci. USA 99, 16438-16445, 2002

Hall IM,* Shankaranarayana GD,* Noma K,* Ayoub N, Cohen A, Grewal SIS. Establishment and maintenance of a heterochromatin domain. Science 297, 2232-2237, 2002, * contributed equally

Noma K, Allis CD, Grewal SIS. Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science 293, 1150-1155, 2001.