Data from: A combination of transcriptional and microRNA regulation improves the stability of the relative concentrations of target genes

It is well known that, under suitable conditions, microRNAs are able to
fine tune the relative concentration of their targets to any desired
value. We show that this function is particularly effective when one of
the targets is a Transcription Factor (TF) which regulates the other
targets. This combination defines a new class of feed-forward loops (FFLs)
in which the microRNA plays the role of master regulator. Using both
deterministic and stochastic equations, we show that these FFLs are indeed
able not only to fine-tune the TF/target ratio to any desired value as a
function of the miRNA concentration but also, thanks to the peculiar
topology of the circuit, to ensure the stability of this ratio against
stochastic fluctuations. These two effects are due to the interplay
between the direct transcriptional regulation and the indirect TF/Target
interaction due to competition of TF and target for miRNA binding (the so
called “sponge effect”). We then perform a genome wide search of these
FFLs in the human regulatory network and show that they are characterized
by a very peculiar enrichment pattern. In particular, they are strongly
enriched in all the situations in which the TF and its target have to be
precisely kept at the same concentration notwithstanding the environmental
noise. As an example we discuss the FFL involving E2F1 as Transcription
Factor, RB1 as target and miR-17 family as master regulator. These FFLs
ensure a tight control of the E2F/RB ratio which in turns ensures the
stability of the transition from the G0/G1 to the S phase in quiescent
cells.