REST regulatory networks Gene Yeo1,2 Stefan Aigner 2,

REST regulatory networks Gene Yeo1,2 Stefan Aigner 2,

REST regulatory networks Gene Yeo1,2 Stefan Aigner 2, Eric Van Nostrand1,2, Fred H. Gage2 1 Crick-Jacobs Center of Theoretical and Computational Biology 2 Laboratory of Genetics The Salk Institute for Biological Studies, La Jolla, CA REST repressor/silencing complex silences neuronal genes in non-neuronal cells Differentiated non-neuronal cells m mK9 mCpG Methyl H3K9 MeCP2 HDAC mSin3

SCP CoREST DNMT1 HMT K9 REST mK9 m m mK9 mK9 m mK9 m RE1 m

m Histone K4 Demethylase HDAC mK9 MeCP2 m m HP1 mK9 mK9 m mK9 REST binds to a ~20 bp sequence REST levels decrease during neuronal differentiation

Slide courtesy of XC REST sites are highly-conserved across evolution Superiorcervical ganglion neuralspecific 10 Synaptosomalassociated protein 25 Brain-derived neurotrophic factor Algorithm to identify conserved REST sites Converged motif Several REST sites are proximal to microRNAs REST-regulated microRNAs are neuronal REST binds in vivo to predicted sites

REST occupancy near microRNA genes decreases during neural differentiation Anti-REST chromatin immunoprecipitation/qPCR for candidate REST sites in P19 cells upon neural induction 0.8 0.7 0.6 Undifferentiated Differentiated 0.5 0.4 0.3 0.2 0.1 0 % of chromatin immunoprecipitated miR-9-3 30e/30c-1 miR135b miR153-1 miR-29a/29b-1 miR219-1 miR192/194-2 miR182/96/183

Neural-specific microRNAs and REST co-repressors during mouse stem cell neuronal differentiation Neural differentiation of P19 mouse embryonic carcinoma cells RA induction Western blots Northern blots d0 d5 d7 d9 d11 miR-9 miR-124a U6 d0 d5 d7 d9 d11 REST msin3A SCP-1 CoREST Neuronal marker TUJ1

Neural-specific microRNAs likely target components of the REST co-repressor complex Plasmid transfected: GFP m mK9 mCpG Plasmid transfected: empty mir-9 msin3A SCP-1 -actin Loading control

em pt m y ir3 m 24 ir1 m ir1 24 mir-9 and mir-124a downregulate mSin3a and SCP-1, respectively Methyl H3K9 MeCP2 HDAC mSin3 HDAC SCP REST

mK9 m m mK9 mK9 m mK9 m RE1 m m Histone K4 Demethylase mK9

CoREST DNMT1 HMT K9 HP1 MeCP2 m m mK9 mK9 m mK9 Neural-specific microRNAs likely target components of the REST corepressor complex A sensor assay confirms predicted target sites for miR-124a in the 3UTR of SCP-1 SCP-1 3UTR SCP-1 sensor ADAR1 3UTR

Control sensor Control sensor SCP1 sensor + mir124 Enhancing neurogenesis mir-124 induces neuronal gene expression in P19 mouse EC cells 6 5 4 24 hours 48 hours 3 2 change Fold (mir124/control) 1

0 GAP43 NFH Glur2 Promoter driving luciferase ND1 A model for REST regulation to enhance neurogenesis Neuronal progenitors REST high Neurons REST low REST-regulated microRNAs ON REST-regulated microRNAs

downregulate components of the REST repressor complex REST-regulated microRNAs OFF REST-regulated protein coding genes OFF Acknowledgements: Eunice Meija, Xinwei Cao REST-regulated protein coding genes ON Supported by Crick-Jacobs Center, NSF

Recently Viewed Presentations

  • The History of Astronomy

    The History of Astronomy

    His model of the Solar System put forth in Introduction to the New Astronomy (1588) combined the geocentric and heliocentric models. In the Tychonic system, the objects on blue orbits (the Moon and the Sun) revolve around the Earth.
  • Informatics 121 Software Design I Lecture 14 Duplication

    Informatics 121 Software Design I Lecture 14 Duplication

    In sum. Understanding all of the design activities that take place in software engineering. Significant shift to this kind of overall approach to software development (innovation, creativity, design)
  • Bacterial Nutrition & Growth - Penn State York

    Bacterial Nutrition & Growth - Penn State York

    Arial Default Design Microsoft Photo Editor 3.0 Photo Environmental Factors Tolerance to All Environmental Factors (Shelford's Law of Tolerance) Cardinal Temperatures Minimum, Optimum, and Maximum Slide 3 Water Activity Quantifies water availability in an environment; decreases with increasing solute concentration.
  • Chi-square Test - Central Catholic High School

    Chi-square Test - Central Catholic High School

    Chi-square Test also called chi-squared or χ2 distribution In statistics, a result is significant if it is unlikely to have occurred by chance. Because maybe you're not being a great scientist and the independent variable (the test condition being examined)...
  • Welcome to the Public Library Annual Report Review

    Welcome to the Public Library Annual Report Review

    Virtual Visits - Number of unique visitors to library's website. Definition: Unique visitors is the number of inferred individual people as determined by IP address (filtered for spiders and robots), within a designated reporting timeframe, with activity consisting of one...
  • WICID (Web-based Interface to Census Interaction Data): A ...

    WICID (Web-based Interface to Census Interaction Data): A ...

    Internet access to UK Census interaction data: that's WICID! John Stillwell Centre for Computational Geography University of Leeds, Leeds LS2 9JT
  • A Level Physics: Electrical Quantities: Resistance and Resistivity

    A Level Physics: Electrical Quantities: Resistance and Resistivity

    charge carriers (current) Conduction . is the . movement of charged particles . or . propagation of energy. through a material. Delta. Conduction. A metal consists of . positive metal ions. with . free electrons. that move with . random...
  • NonFiction - Tamaqua Area School District

    NonFiction - Tamaqua Area School District

    The use of fictional techniques when writing a piece of nonfiction. It is a true, well-researched, journalistically-sound story written with vivid descriptions and narrative flow. Opinion Piece. Writing about a particular topic that expresses the personal view, attitude, or appraisal...