TY - JOUR
T1 - The exosome complex establishes a barricade to erythroid maturation
AU - McIver, Skye C.
AU - Kang, Yoon A.
AU - Devilbiss, Andrew W.
AU - O'Driscoll, Chelsea A.
AU - Ouellette, Jonathan N.
AU - Pope, Nathaniel J.
AU - Camprecios, Genis
AU - Chang, Chan Jung
AU - Yang, David
AU - Bouhassira, Eric E.
AU - Ghaffari, Saghi
AU - Bresnick, Emery H.
N1 - Publisher Copyright:
© 2014 by The American Society of Hematology.
PY - 2014/10/2
Y1 - 2014/10/2
N2 - Complex genetic networks control hematopoietic stem cell differentiation into progenitors that give rise to billions of erythrocytes daily. Previously, we described a role for the master regulator of erythropoiesis, GATA-1, in inducing genes encoding components of the autophagy machinery. In this context, the Forkhead transcription factor, Foxo3, amplified GATA-1-mediated transcriptional activation. To determine the scope of the GATA-1/Foxo3 cooperativity, and to develop functional insights, we analyzed the GATA-1/Foxo3-dependent transcriptome in erythroid cells. GATA-1/Foxo3 repressed expression of Exosc8, a pivotal component of the exosome complex, which mediates RNA surveillance and epigenetic regulation. Strikingly, downregulating Exosc8, or additional exosome complex components, in primary erythroid precursor cells induced erythroid cell maturation. Our results demonstrate a new mode of controlling erythropoiesis in which multiple components of the exosome complex are endogenous suppressors of the erythroid developmental program. (Blood. 2014;124(14):2285-2297).
AB - Complex genetic networks control hematopoietic stem cell differentiation into progenitors that give rise to billions of erythrocytes daily. Previously, we described a role for the master regulator of erythropoiesis, GATA-1, in inducing genes encoding components of the autophagy machinery. In this context, the Forkhead transcription factor, Foxo3, amplified GATA-1-mediated transcriptional activation. To determine the scope of the GATA-1/Foxo3 cooperativity, and to develop functional insights, we analyzed the GATA-1/Foxo3-dependent transcriptome in erythroid cells. GATA-1/Foxo3 repressed expression of Exosc8, a pivotal component of the exosome complex, which mediates RNA surveillance and epigenetic regulation. Strikingly, downregulating Exosc8, or additional exosome complex components, in primary erythroid precursor cells induced erythroid cell maturation. Our results demonstrate a new mode of controlling erythropoiesis in which multiple components of the exosome complex are endogenous suppressors of the erythroid developmental program. (Blood. 2014;124(14):2285-2297).
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U2 - 10.1182/blood-2014-04-571083
DO - 10.1182/blood-2014-04-571083
M3 - Article
C2 - 25115889
AN - SCOPUS:84907687722
SN - 0006-4971
VL - 124
SP - 2285
EP - 2297
JO - Blood
JF - Blood
IS - 14
ER -