Papers by Michael Greenberg
Nature Reviews Neuroscience, Nov 23, 2017
Excitation-transcription coupling shapes network formation during brain development and controls ... more Excitation-transcription coupling shapes network formation during brain development and controls neuronal survival, synaptic function and cognitive skills in the adult. New studies have uncovered differences in the transcriptional responses to synaptic activity between humans and mice. These differences are caused both by the emergence of lineagespecific activity-regulated genes and by the acquisition of signal-responsive DNA elements in gene regulatory regions that determine the extent to which transcription can be induced by synaptic activity. Such evolutionary divergence may have contributed to lineage-related advancements in cognitive abilities. The basic brain structures and anatomical connectivities that enable perception, motor function, social behavior and cognitive skills are similar in mice and humans. However, in the 80-100 million years since the last common ancestor of these two species, human brain complexity and circuit organization has diverged substantially from that of mice, coinciding with the development of superior intellectual abilities in humans 1-3 . The prevailing view is that, in mammals, such phenotypic divergence has been driven primarily by changes in the relative expression levels of genes 4 , rather than by differences in their coding regions. This hypothesis, which is over 40 years old 5 , is grounded in the observation that there are substantial biological differences between species, despite conservation of protein sequences 5 and is supported by recent genome-wide comparative transcriptome analyses that have demonstrated humanspecific gene expression networks in the brain and elsewhere . The evolutionary changes in gene expression that have supported progression towards an increased cognitive repertoire in humans may have been caused by alterations in regulatory DNA regions, such as promoters and enhancers. Indeed, one study showed that forebrainspecific enhancers that are active in early development show high levels of evolutionary
Nature reviews. Neuroscience, 2018
Excitation-transcription coupling shapes network formation during brain development and controls ... more Excitation-transcription coupling shapes network formation during brain development and controls neuronal survival, synaptic function and cognitive skills in the adult. New studies have uncovered differences in the transcriptional responses to synaptic activity between humans and mice. These differences are caused both by the emergence of lineage-specific activity-regulated genes and by the acquisition of signal-responsive DNA elements in gene regulatory regions that determine whether a gene can be transcriptionally induced by synaptic activity or alter the extent of its inducibility. Such evolutionary divergence may have contributed to lineage-related advancements in cognitive abilities.
Nature Neuroscience, Sep 7, 2014
Neuron, Jan 24, 2018
Gene transcription is the process by which the genetic codes of organisms are read and interprete... more Gene transcription is the process by which the genetic codes of organisms are read and interpreted as a set of instructions for cells to divide, differentiate, migrate, and mature. As cells function in their respective niches, transcription further allows mature cells to interact dynamically with their external environment while reliably retaining fundamental information about past experiences. In this Review, we provide an overview of the field of activity-dependent transcription in the vertebrate brain and highlight contemporary work that ranges from studies of activity-dependent chromatin modifications to plasticity mechanisms underlying adaptive behaviors. We identify key gaps in knowledge and propose integrated approaches toward a deeper understanding of how activity-dependent transcription promotes the refinement and plasticity of neural circuits for cognitive function.
Molecular cell, Dec 21, 2017
Enhancer elements are genomic regulatory sequences that direct the selective expression of genes ... more Enhancer elements are genomic regulatory sequences that direct the selective expression of genes so that genetically identical cells can differentiate and acquire the highly specialized forms and functions required to build a functioning animal. To differentiate, cells must select from among the ∼106 enhancers encoded in the genome the thousands of enhancers that drive the gene programs that impart their distinct features. We used a genetic approach to identify transcription factors (TFs) required for enhancer selection in fibroblasts. This revealed that the broadly expressed, growth-factor-inducible TFs FOS/JUN (AP-1) play a central role in enhancer selection. FOS/JUN selects enhancers together with cell-type-specific TFs by collaboratively binding to nucleosomal enhancers and recruiting the SWI/SNF (BAF) chromatin remodeling complex to establish accessible chromatin. These experiments demonstrate how environmental signals acting via FOS/JUN and BAF coordinate with cell-type-specif...
Nature, 2010
We used genome-wide sequencing methods to study stimulus-dependent enhancer function in neurons. ... more We used genome-wide sequencing methods to study stimulus-dependent enhancer function in neurons. We identified ∼12,000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator CBP in an activity-dependent manner. A function of CBP at
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Papers by Michael Greenberg