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2017 ; 51
(ä): 47-62
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Epo reprograms the epigenome of erythroid cells
#MMPMID28410882
Perreault AA
; Benton ML
; Koury MJ
; Brandt SJ
; Venters BJ
Exp Hematol
2017[Jul]; 51
(ä): 47-62
PMID28410882
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The hormone erythropoietin (Epo) is required for erythropoiesis, yet its
molecular mechanism of action remains poorly understood, particularly with
respect to chromatin dynamics. To investigate how Epo modulates the erythroid
epigenome, we performed epigenetic profiling using an ex vivo murine cell system
that undergoes synchronous erythroid maturation in response to Epo stimulation.
Our findings define the repertoire of Epo-modulated enhancers, illuminating a new
facet of Epo signaling. First, a large number of enhancers rapidly responded to
Epo stimulation, revealing a cis-regulatory network of Epo-responsive enhancers.
In contrast, most of the other identified enhancers remained in an active
acetylated state during Epo signaling, suggesting that most erythroid enhancers
are established at an earlier precursor stage. Second, we identified several
hundred super-enhancers that were linked to key erythroid genes, such as Tal1,
Bcl11a, and Mir144/451. Third, experimental and computational validation revealed
that many predicted enhancer regions were occupied by TAL1 and enriched with
DNA-binding motifs for GATA1, KLF1, TAL1/E-box, and STAT5. Additionally, many of
these cis-regulatory regions were conserved evolutionarily and displayed
correlated enhancer:promoter acetylation. Together, these findings define a
cis-regulatory enhancer network for Epo signaling during erythropoiesis, and
provide the framework for future studies involving the interplay of epigenetics
and Epo signaling.
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