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2014 ; 28
(7
): 989-98
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Minireview: pioneer transcription factors in cell fate specification
#MMPMID24825399
Drouin J
Mol Endocrinol
2014[Jul]; 28
(7
): 989-98
PMID24825399
show ga
The specification of cell fate is critical for proper cell differentiation and
organogenesis. In endocrine tissues, this process leads to the differentiation,
often a multistep process, of hormone-producing cells. This process is driven by
a combination of transcription factors (TFs) that includes general factor,
tissue-restricted, and/or cell-restricted factors. The last 2 decades have seen
the discovery of many TFs of restricted expression and function in endocrine
tissues. These factors are typically critical for expression of hormone-coding
genes as well as for differentiation and proper function of hormone-producing
cells. Further, genes encoding these tissue-restricted TFs are themselves subject
to mutations that cause hormone deficiencies. Although the model that emerged
from these 2 decades is one in which a specific combination of TFs drives a
unique cell specification and genetic program, recent findings have led to the
discovery of TFs that have the unique property of being able to remodel chromatin
and thus modify the epigenome. Most importantly, such factors, known as pioneer
TFs, appear to play critical roles in programming the epigenome during the
successive steps involved in cell specification. This review summarizes our
current understanding of the mechanisms for pioneer TF remodeling of chromatin.
Currently, very few TFs that have proven pioneer activity are known, but it will
be critical to identify these factors and understand their mechanisms of action
if we are to harness the potential of regenerative therapies in endocrinology.
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