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SUMMARY:Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain
  - Joseph R Ecker PhD\, The Salk Institute for Biological Studies\, La Jol
 la\, CA
DTSTART:20180419T120000Z
DTEND:20180419T130000Z
UID:TALK74351@talks.cam.ac.uk
CONTACT:Kate Davenport
DESCRIPTION:DNA methylation is a chemical modification that occurs predomi
 nantly on CG dinucleotides in mammalian genomes. However\, recent studies 
 from our laboratory have revealed that non-CG methylation (mCH) is more ab
 undant than CG methylation and non-randomly distributed in the genomes of 
 brain cells. mCH accumulates during the establishment of neural circuits a
 nd is associated with Rett syndrome.  A comprehensive understanding of how
  neural circuits spanning the entire brain generate the full repertoire of
  perception and behaviors requires a list of brain cell types\, as well th
 e means to target each cell type in order to interrogate the functional in
 teractions that give rise to the emergent properties of the whole system. 
  Neuronal diversity is essential for mammalian brain function but poses a 
 challenge to molecular profiling. To facilitate cell-type-specific epigeno
 mic studies\, we have developed approaches to isolate nuclei from subtypes
  of neocortical neurons\, revealing highly distinctive epigenomic landscap
 es. Hundreds of thousands of regions differ in chromatin accessibility and
  DNA methylation signatures characteristic of gene regulatory regions whic
 h are predicted to bind distinct cohorts of neuron subtype-specific transc
 ription factors. Surprisingly\, neuronal epigenomes reflect both past and 
 present gene expression\, with DNA hyper-methylation at developmentally cr
 itical genes appearing as a novel epigenomic signature in mature neurons. 
 More recently\, we have developed single cell methylome profiling methods 
 that now allow an unbiased census of the diversity of neuronal cell types 
 in the mammalian brain. We are using these approaches to begin to link the
  functional and transcriptional complexity of neurons throughout the brain
  to their underlying epigenomic diversity.\n\n
LOCATION:CRUK CI Lecture Theatre
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