More work will have to be done to establish how higher order chromatin changes, epigenetic modifications and tissue-specific transcription factors interact in cell fate determination and in diseases, e. g. in hematopoietic development or the skin. Recent interesting reviews: Conaway et al., 2012; Portela et al., 2010

There is no such specific answer to your question there are numerous unsolved problems, like siRNA biogenesis why genome need siRNAs when they have miRNA. how methylation occurs in genome (any patterns?) role of repeats in DNA methylation. Histone modifications which enzymes and proteins are involved in it. How proteins interact with DNA how proteins interact with other proteins. As I said there is no specific answer, answer to one question arises multiple questions. One can read the above mentioned articles also a review by He et al (PMID 21321601) is one of the most comprehensive review of DNA methylation.

I think the major area of interest is the way in which chromatin, DNA methylation and non-coding RNAs cooperate to control gene expression and cell phenotype.

A large number of cancers have been profiled for epigenetic marks and what is now needed is more understanding of functional relationships.  I think the signalling links between environment and chromatin changes have been a recent breakthrough -- and that we should now explore whether long range chromatin interactions could also be mediated by nuclear signalling perhaps even independently of 3C interactions.