Modelling and global analysis of transcript profiles reveals dynamic roles for microRNAs in transcriptional networks controlling lineage commitment.

Controlled maintenance of multipotent stem cells is a key component for the
development and sustainment of complex multicellular organisms. Various
signalling pathways contribute to these processes being either lineage specific or
more ubiquitously distributed over different tissue types. Transcription factors are
considered as the primary propagators of signals that induce multipotent precursor
cells to differentiate into specified cell types. These processes are required to
revolve in a constrained and timely manner, with different cell types using variable
sets of transcription factors and time scales. microRNA molecules represent an
efficient and specific class of regulatory non-coding RNA molecules that efficiently
constrain and specify differentiation cascades. New findings suggest that various
endogenous non-coding RNA species, whose expression is governed through
elaborate transcription factor networks, contribute to the regulation of genomewide
transcriptional output. Here, evidence is presented of microRNA and
transcription factor connectivity during differentiation cascades. First, these two
classes of RNA regulatory molecules are shown to share a common target,
lipoprotein lipase, and exert dynamical regulation over its expression during
adipogenic differentiation. Second, investigating the genome-wide initial events of
adipogenic and osteoblastic lineage commitment cascades reveals extensive
transcription in non-protein-coding genomic regions. Further analysis of a select
cohort of these non-coding transcripts allows for inferring transcription factor
binding dynamics through enhancer-related RNA sequences as well as suggests a
more wide-spread role for long non-coding RNA species in regulating
transcriptional output. These findings contribute to unravelling basic
transcriptional circuitry during cellular transitions.