Douglas L. Chalker, Ph.D.


Molecular Genetics and Genomics Program
Molecular Microbiology and Microbial Pathogenesis Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-935-8838

  • 314-935-7143

  • 314-935-4432

  • 304 Bayer Laboratory of the Life Sciences



  • chromatin structure, development, DNA, genome rearrangements, RNA interference, transcription

  • Genetic and epigenetic regulation of developmentally programmed DNA rearrangements of Tetrahymena

Research Abstract:

RNA interference (RNAi)-related mechanisms participate in diverse epigenetic phenomena. Few are more extreme than the genome remodeling of the ciliate Tetrahymena thermophila. This organism eliminates nearly 15 megabases of its germline DNA from the somatic nucleus during its development. Our lab aims to understand the regulation of this massive genome reorganization using a combination of genetic, molecular, and cellular biology approaches to uncover how ~6000 DNA segments are selectively excised. Our current model is built on the observations that bi-directional germline transcription leads to the generation of 28-30 base RNA molecules (scan RNAs) that then target specific chromatin modification(s) to the homologous locus. The DNA rearrangement machinery recognizes the modified chromatin state and eliminates the targeted DNA segment. These studies will certainly provide fundamental insight into RNAi-related mechanisms that direct chromatin modifications that are critical for transcriptional gene silencing and heterochromatin formation in eukaryotes. Underlying this proposal is a goal to understand how RNA molecules can communicate genetic information between the parental and developing genomes, which has great potential to reveal novel roles for RNA in epigenetic programming. Additionally, we believe many of the DNA segments targeted for elimination are important for germline chromosome structure, and thus understanding how the cell specifically recognizes these sequences will contribute general knowledge of mechanisms ensuring chromosome stability that are essential to prevent aberrant rearrangements.

Selected Publications:

Motl, JA and DL Chalker. (2011) Zygotic Expression of the Double-Stranded RNA Binding Motif Protein, Drb2p, is required for DNA Elimination in the Ciliate, Tetrahymena thermophila. Eukaryot. Cell 10(12):1648-1659.

Chalker, DL and M-C Yao (2011) DNA ELIMINATION IN CILIATES: Transposon Domestication and Genome Surveillance. Annu. Rev. Genet. 2011. 45:227-46.

Fass, J. N., N. A. Joshi, M. T. Couvillion, J. Bowen, M. A. Gorovsky, E. P. Hamilton, E. Orias, K. Hong, R. S. Coyne, J. A. Eisen, D. L. Chalker, D. Lin, and K. Collins. (2011). Genome-scale analysis of programmed DNA elimination sites in Tetrahymena thermophila G3 1:515-522.

Matsuda A, Shieh AW, Chalker DL, Forney JD. (2010) The conjugation-specific Die5 protein is required for development of the somatic nucleus in both Paramecium and Tetrahymena. Eukaryot Cell. 9:1087-1099.

Chalker DL. Dynamic nuclear reorganization during genome remodeling of Tetrahymena. Biochim Biophys Acta. 2008 Nov 1783(11):2130-6.

Malone CD, Falkowska KA, Li AY, Galanti SE, Kanuru RC, LaMont EG, Mazzarella KC, Micev AJ, Osman MM, Piotrowski NK, Suszko JW, Timm AC, Xu MM, Liu L, Chalker DL. Nucleus-specific importin alpha proteins and nucleoporins regulate protein import and nuclear division in the binucleate Tetrahymena thermophila. Eukaryot Cell. 2008 7:1487-99.

Rexer CH and Chalker DL. Lia1p, a Novel Protein Required during Nuclear Differentiation for Genome-Wide DNA Rearrangements in Tetrahymena thermophila Eukaryotic Cell 2007 6(8):1320-1329.

Yao M-C, Yao C-H, Halasz LM, Fuller P, Rexer CH, Wang SH, Jain R, Coyne RS and Chalker DL. Identification of novel chromatin-associated proteins involved in programmed genome rearrangements in Tetrahymena. J. Cell. Sci 2007 120(9): 1978-89.

Malone CD, Anderson AM, Motl JA, Rexer CH and Chalker DL. Germline transcripts are processed by a Dicer-like protein that is essential for developmentally programmed genome rearrangements of Tetrahymena thermophila. Mol. Cell. Biology 2005 25(20):9151-64.

Last Updated: 8/6/2012 9:56:11 AM

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