[caption id="attachment_2583" align="alignright" width="216" caption="Copyright: dolgachov / 123RF Stock Photo"][/caption]
When you were commuting to work this morning, maybe you listened to the traffic report on the radio. And that's often helpful. But you probably heard a lot about cars and roads that may, or may not affect your commute. If you had a GPS traffic app on your phone, you could see current traffic on your own personal route. Improved technology improves your efficiency. And so it is with studies of chromatin regulation.
Chromatin regulation is a dynamic combination of effects that are highly tissue,... and even cell specific. Yet many currents methods require data on each chromatin feature to be generated separately from different sample sets, (i.e. ChIP-seq or BS-seq).
The review article;Hyun BR, McElwee JL, Soloway PD, (2014) Single molecule and single cell epigenomics [Methods], details the current state of affairs in the development of single molecule and single cell analysis methods for epigenetics. The hope is that direct characterization methods will eliminate variables and enhance our understanding.
[caption id="attachment_2566" align="aligncenter" width="300" caption=" Figure 1. DNA methylation changes in autistic cerebral cortex regions. S Nardone et al. Translational Psychiatry, September, 2014. 10.1038/tp.2014.70"][/caption]
A mystery about the human brain is how its many regions develop and perform in unison. We are normally so blissfully unaware of our minds' abilities, aren't we?!!! Autism spectrum disorders show us how deficits in specific brain skills can cumulate to difficulties in communicating, learning, socializing and sensory perception.
Forty six percent of the U.S. increase in ASD diagnoses, are calculated to be based on unknown environmental causes. Immunity challenges during critical prenatal periods have already been linked to ASD development. Now researchers from Bar Ilan University in Israel, have produced solid “links” of epigenetic data to form a causal “chain” between immune response and autism.
In the paper, "DNA methylation analysis of the autistic brain reveals multiple dysregulated biological pathways. S. Nardone et al. (2014)Nature Translational Psychiatry", the researchers used sodium bisulfite sequencing microarray / Illumina 450 K methylation array to probe brain tissue DNA methylomes. The samples were from the prefrontal cortex (12 cases & 12 controls), and the anterior cingulate gyrus (11 cases & controls). All samples were matched for age and postmortem time.
Here are some of their findings:
1. Methylomes were overall “less region-specific identity” in autism.
2. Low-density CpG areas, (known to be more dynamic during development), had the most differentially methylated sites between normal and ASD brain tissues.
3. ASD methylome signatures were related primarily to immune response - including leukocyte migration, positive regulation of cytokine biosynthetic process and inflammatory response to antigens.
Now I had no idea about this myself, but apparently many of these classical immune response genes have roles in microglial cell fate specification and synaptic pruning during development. It's not clear yet exactly how expression is mis-regulated in neurons vs. microglial cell types.
Its all quite exciting to get a peek into epigenetic regulation of brain development. We know that people's brain methyolomes change into young adulthood. This plasticity alone gives us hope to help individuals affected by ASD to meet their potential.