BBS Faculty Member - Danesh Moazed

Danesh Moazed

Department of Cell Biology

Harvard Medical School / HHMI
LHRRB, Room 517
240 Longwood Avenue
Boston, MA 02115
Tel: 617-432-1258
Email: danesh@hms.harvard.edu
Lab Members: 7 postdoctoral fellows, 3 graduate students
Visit my lab page here.



We are interested in epigenetic mechanisms that control cellular memory and genome stability in eukaryotes and use yeast and mammalian cells as model systems to study these mechanisms.

We study how heterochromatin, a silent chromatin structure that regulates gene expression and genome stability, is established and epigenetically inherited. We have uncovered how nuclear RNAi participates in various aspects of heterochromatin formation from its assembly to its epigenetic inheritance. Our work has demonstrated that RNAi complexes localize to nascent noncoding RNAs at chromosome regions that are assembled into heterochromatin. This localization leads to co-transcriptional degradation of heterochromatic RNAs and also directly recruits downstream chromatin-modifying complexes that establish heterochromatin. In addition, we have shown that heterochromatin recruits other RNA degradation enzymes that play a critical role in keeping it completely silent. Our studies in this area have used fission yeast as a model system, but nuclear RNAi and RNA processing pathways also play broad and conserved roles in chromatin regulation in other eukaryotes.

Our work on epigenetic inheritance mechanisms has provided evidence that positive feedback mechanisms associated with histone post-translational modifications (PTMs) can mediate epigenetic inheritance. However, in wild-type cells, histone PTM positive feedback appears to be too weak to maintain epigenetic memory. We have shown that histone PTMs work together with specific DNA sequences to maintain epigenetic memory and would like to understand how DNA sequence contributes to epigenetics. We continue to use fission yeast, as well as mammalian cells, as a model systems to explore the roles of DNA sequence, noncoding RNA, RNA processing pathways, and histone modifications in epigenetic processes.



Last Update: 6/28/2017



Publications

For a complete listing of publications click here.

 


 

Jain R, Iglesias N, Moazed D (2016). Distinct functions of Argonaute slicer in siRNA maturation and heterochromatin formation. Mol Cell 63, 191-205.

Behrouzi R, Lu C, Currie MA, Jih G, Iglesias N, Moazed D (2016). Heterochromatin assembly by interrupted Sir3 bridges across neighboring nucleosomes.
Elife 2016; 10.7554/eLife.17556.

Mathew RS, Tatarakis A, Rudenko A, Johnson-Venkatesh E, Yang YJ, Murphy E, Todd TP, Schepers SP, Siuti N, Martorell AJ, Falls WA, Hammack SE, Walsh CA, Tsai L-H, Umemori H, Bouton ME, Moazed D. (2016). A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory.
eLife 2016;10.7554/eLife.22467.

Wang X, Moazed D (2017). DNA sequence-dependent mechanism for epigenetic inheritance of H3K9 methylation.
Science 356, 88-91.

Jih G, Iglesias N, Currie MA, Bhanu NV, Paulo JA, Gygi SP, Garcia B, Moazed D (2017). Unique roles for histone H3K9me states in RNAi and heritable silencing of transcription.
Nature doi:10.1038/nature23267.



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