September 22, 2012

Steric versus chemical adduct model of epigenetics. Developmental epigenetics. Disorderly proteins?

Might steric approach be more dominant than just a chemical adduct  model (such as methylation or deacetylation etc. for gene suppression) of epigenetic regulation of protein coding genes?

For example, statistically might one initially have successive pulses of short interfering RNA (iRNA), each with greater specificity for various weak sites of genome? Might this be in analogy to antibodies’ increasing specificity over time for exposure to a given antigen? Initially wedging open, might one have weak points in overall continuously (?) flexing chromatin structure? Then other successive pulses of iRNA of greater specificity, statistically but for more specific sites, and then eventually transcription factor, and transcription factor complex, fitting at DNA site of gene? Empirically, perhaps use input of various amounts of iRNA, of varying homogeneity and for various conditions, and measure just protein content output (measure of any protein coding gene transcription), or measure RNAseq (sequencing); then model what might be happening?

Might much of non-coding DNA relate to developmental regulation? That is, if yeast, C. elegans i.e. nematode, and us all have ~20,000 genes with 2^20,000 possibilities, then might different phenotypes relate more to gene expression and regulation by non-coding DNA and siRNA etc. for unfolding ontological development, rather than such non-coding DNA just relating to adult gene epigenetic expression/repression? Wherein for the latter perhaps might one have just 2^2000 genes expressed?

Also analogously, might epigenetics in general, or specifically non-coding RNA (siRNA, riboswitches etc.), function like disorderly proteins exploring many different binding site configurations for possible interactions? Supposedly some such disorderly proteins can maintain such shifting interaction at a given site, even after bound.  TMM

Guttman Mitchell, Rinn John L., Modular regulation of large non-coding RNAs, Nature 482, p.339, Feb. 16, 2012.

Chouard Tanguy, Breaking the Protein Rules, Nature 471, p. 151, March 10, 2011.

Reviews: Protein Dynamics, Science Vol 324, April 10, 2009, p.197.

Lee, Jeannie T., Epigenetic Regulation by Long non-coding (lnc) RNAs, Science vol 338, Dec. 14, 2012, p. 1435.

Alvaro Sanchez, Ido Golding, Genetic Determinants and Cellular Constraints in Noisy Gene Expression, Science  December 6 2013: 1188-1193.


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