Table 1.

The multi-scale DNA methylome.

Process type	Genomic scale	Cellular scale	Spatial scale	Time scale	Examples	Potential permissive/instructive for learning and memory	References
Constitutive	Genome-wide	All adult cells	Brain-wide	Weeks/Years (lifespan)	Repressive role of promoter mCG	Permissive
	Genome-wide	Neurons	Brain-wide	Weeks/Years (lifespan)	Accumulation of mCH	Permissive? Or no role?	Xie et al., 2012; Lister et al., 2013
					Accumulation of hmCG		Kriaucionis and Heintz, 2009; Szulwach et al., 2011; Mellén et al., 2012
	Genome-wide			Dynamic (hours?)	Reduction of global mC following neuronal depolarization or fear conditioning	Likely permissive	Ma et al., 2009; Guo et al., 2011a
	Chromosomal	All adult cells	Brain-wide	Weeks/Years (lifespan)	X-inactivation	Permissive	Lee and Bartolomei, 2013
	Megabase	All adult cells	Brain-wide	Weeks/Years (lifespan)	Differentially methylated valleys (DMVs); mCH deserts	Permissive	Xie et al., 2013
	500 bp	Specific neuron or glial cell types	Brain-wide	Weeks/Years (lifespan)	Cell type DMRs	Permissive + Instructive?	Lister et al., 2013; Ziller et al., 2013
	500 bp	Specific neuron or glial cell types	Local brain region	Weeks/Years (lifespan)	Cell type and regional DMRs	Permissive + Instructive?
	500 bp	Individual cells	Local	Dynamic (hours?)	Activity-dependent DMRs	Potentially Instructive?	Lubin et al., 2008; Miller et al., 2010; Guo et al., 2011a,b; Mizuno et al., 2012; Baker-Andresen et al., 2013; Day et al., 2013
					Dynamic methylation at Reln, CaN, Egr1		Miller et al., 2010
	500 bp?	Individual cells		Dynamic (hours?)	Activity-dependent 5hmC (DhMRs)		Hahn et al., 2013; Li et al., 2014
Local	10 bp	Specific neuron or glial cell types		Weeks/Years (lifespan)	Demethylation at (activity-dependent or independent) transcription factor binding sites	Potentially instructive?	Guo et al., 2011b

Examples of DNA methylation features that exist at different spatio-temporal scales.