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2017 ; 6
(12
): 2106-2114
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Concise Review: Epigenetic Regulation of Hematopoiesis: Biological Insights and
Therapeutic Applications
#MMPMID29080249
Antoniani C
; Romano O
; Miccio A
Stem Cells Transl Med
2017[Dec]; 6
(12
): 2106-2114
PMID29080249
show ga
Hematopoiesis is the process of blood cell formation starting from hematopoietic
stem/progenitor cells (HSPCs). The understanding of regulatory networks involved
in hematopoiesis and their impact on gene expression is crucial to decipher the
molecular mechanisms that control hematopoietic development in physiological and
pathological conditions, and to develop novel therapeutic strategies. An
increasing number of epigenetic studies aim at defining, on a genome-wide scale,
the cis-regulatory sequences (e.g., promoters and enhancers) used by human HSPCs
and their lineage-restricted progeny at different stages of development. In
parallel, human genetic studies allowed the discovery of genetic variants mapping
to cis-regulatory elements and associated with hematological phenotypes and
diseases. Here, we summarize recent epigenetic and genetic studies in
hematopoietic cells that give insights into human hematopoiesis and provide a
knowledge basis for the development of novel therapeutic approaches. As an
example, we discuss the therapeutic approaches targeting cis-regulatory regions
to reactivate fetal hemoglobin for the treatment of ?-hemoglobinopathies.
Epigenetic studies allowed the definition of cis-regulatory sequences used by
human hematopoietic cells. Promoters and enhancers are targeted by transcription
factors and are characterized by specific histone modifications. Genetic variants
mapping to cis-regulatory elements are often associated with hematological
phenotypes and diseases. In some cases, these variants can alter the binding of
transcription factors, thus changing the expression of the target genes.
Targeting cis-regulatory sequences represents a promising therapeutic approach
for many hematological diseases. Stem Cells Translational Medicine
2017;6:2106-2114.
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