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
Lab Members: 9 postdoctoral fellows, 4 graduate students
Visit my lab page here.

We are interested in epigenetic mechanisms that control cell identity and chromosome stability in eukaryotes and use the budding and fission yeasts as model systems to study these mechanisms.

Our current work in budding yeast is focused on the SIR silencing complex, which is composed of histone-modifying and histone-binding subunits. We wish to understand (1) how the SIR complex associates with the chromatin fiber to create silenced nucleosomes, (2) how interactions between SIR subunits and histones mediate the spreading of silencing away from initial sites of SIR recruitment, and (3) the mechanism of epigenetic inheritance of silencing and its relationship to various modes of SIR complex recruitment. We use primarily biochemical and structural approaches including fluorescence binding measurements, X ray crystallography, and single molecule cryo-electron microscopy to study these problems.

Our work in fission yeast is focused on the role of noncoding RNAs in assembly and inheritance of heterochromatin. Previously, we identified the RNA-induced transcriptional silencing (RITS) complex and demonstrated a direct role for RNA interference (RNAi) in heterochromatin assembly. Our subsequent analysis and identification of other RNAi and heterochromatin complexes led to the discovery that short interfering RNAs (siRNAs) target nascent noncoding RNAs and use them as templates for the recruitment of the histone methyltransferase complex that initiates heterochromatin formation. This nascent transcript model represents a major paradigm shift in gene regulation mechanisms, which previously involved the targeting of DNA by site-specific DNA-binding proteins. To gain a deeper understanding into the roles of nascent transcripts in chromatin regulation, we would like to define the properties of nascent transcripts and their co-transcriptional RNA processing that allow them to act as scaffolds for chromatin modifying enzymes.

More recently, we provided definitive evidence for the idea that histones and their post-translational modifications can act as carriers of epigenetic information. Our newly developed ectopic heterochromatin assembly systems, which separate the establishment and maintenance steps of heterochromatin formation, provides a unique opportunity to specifically analyze the pathways that mediate chromatin- and noncoding RNA-based epigenetic inheritance.

In addition to our work in yeast, we are beginning to study how the microRNA pathway regulates changes in synaptic plasticity associated with memory and neurodegenerative disease in the mammalian brain.

Last Update: 8/10/2015


For a complete listing of publications click here.



Yu R, Jih G, Iglesias N, Moazed D (2014). Determinants of Heterochromatic siRNA Biogenesis and Function. Mol Cell 53, 262–276.

Eagan ED, Braun CR, Gygi SP, Moazed D (2014). Post-transcriptional regulation of meiotic genes by a nuclear RNA silencing complex.
RNA 20, 867–881.

Ragunathan K, Jih G, Moazed D (2015). Epigenetic inheritance uncoupled from sequence-specific recruitment.
Science 348(6230):1258699.

Holoch D, Moazed D (2015). Small RNA loading licenses Argonaute for assembly into a transcriptional silencing complex.
Nature Structural Molecular Biology 22, 328-35.

© 2015 by the President and Fellows of Harvard College