Pleiotropic role of histone deacetylases in the regulation of human adult erythropoiesis

Yamamura, Kentaro; Ohishi, Kohshi; Katayama, Naoyuki; Zi, Yu; Kato, Kyozo; Masuya, Masahiro; Fujieda, Atsushi; Sugimoto, Yuka; Miyata, Eri; Shibasaki, Tetsunori; Heike, Yuji; Takaue, Yoichi; Shiku, Hiroshi

doi:10.1111/j.1365-2141.2006.06275.x

Cited by 26 publications

(25 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In red cells, HDAC negatively regulate the interleukin-3-mediated growth of early erythroid precursors by suppressing their responsiveness to interleukin-3, and play an important role in erythropoietin-mediated differentiation and survival of erythroid precursors. 20 HDAC also play critical roles in terminal erythropoiesis. Popova et al recently demonstrated that the activities of HDAC are required for chromatin condensation in Friendvirus infected murine spleen erythroblasts (FVA cells).…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase 2 is required for chromatin condensation and subsequent enucleation of cultured mouse fetal erythroblasts

Ji¹,

Yeh²,

Ramı́rez³

et al. 2010

Haematologica

View full text Add to dashboard Cite

The online version of this article has a Supplementary Appendix. BackgroundDuring the final stages of differentiation of mammalian erythroid cells, the chromatin is condensed and enucleated. We previously reported that Rac GTPases and their downstream target, mammalian homolog of Drosophila diaphanous 2 (mDia2), are required for enucleation of in vitro cultured mouse fetal liver erythroblasts. However, it is not clear how chromatin condensation is achieved and whether it is required for enucleation. Design and MethodsMouse fetal liver erythroblasts were purified from embryonic day 14.5 pregnant mice and cultured in erythropoietin-containing medium. Enucleation was determined by flow-cytometry based analysis after treatment with histone deacetylase inhibitors or infection with lentiviral short harirpin RNA. ResultsWe showed that histone deacetylases play critical roles in chromatin condensation and enucleation in cultured mouse fetal liver erythroblasts. Enzymatic inhibition of histone deacetylases by trichostatin A or valproic acid prior to the start of enucleation blocked chromatin condensation, contractile actin ring formation and enucleation. We further demonstrated that histone deacetylases 1, 2, 3 and 5 are highly expressed in mouse fetal erythroblasts. Short hairpin RNA down-regulation of histone deacetylase 2, but not of the other histone deacetylases, phenotypically mimicked the effect of trichostatin A or valproic acid treatment, causing significant inhibition of chromatin condensation and enucleation. Importantly, knock-down of histone deacetylase 2 did not affect erythroblast proliferation, differentiation, or apoptosis. ConclusionsThese results identify histone deacetylase 2 as an important regulator, mediating chromatin condensation and enucleation in the final stages of mammalian erythropoiesis.Key words: histone deacetylase 2, HDAC2, chromatic condensation, enucleation, mammalian erythropoiesis. Haematologica 2010;95(12):2013-2021. doi:10.3324/haematol.2010 Histone deacetylase 2 is required for chromatin condensation and subsequent enucleation of cultured mouse fetal erythroblasts © F e r r a t a S t o r t i F o u n d a t i o n Citation: Ji P, Yeh V, Ramirez T, Murata-Hori M, and Lodish HF. Histone deacetylase 2 is required for chromatin condensation and subsequent enucleation of cultured mouse fetal erythroblasts.

show abstract

Section: Introductionmentioning

confidence: 99%

Histone deacetylase 2 is required for chromatin condensation and subsequent enucleation of cultured mouse fetal erythroblasts

Ji¹,

Yeh²,

Ramı́rez³

et al. 2010

Haematologica

View full text Add to dashboard Cite

show abstract

“…Valproic acid (VPA), a non-selective HDACI, was reported to sustains the expression of stemness-related markers in hematopoietic stem/progenitor cells and enhance erythrocyte and megakaryocyte differentiation, by up-regulating genes of growth factor-independent protein 1B (GFI1B) and mixed-lineage leukemia translocated to chromosome 3 protein (MLLT3), mediated by the histone hyperacetylation at their promoter sites 49 . HDACIs FK228 and VPA also enhances the potential of interleukin-3 to stimulate erythropoiesis and megakaryopoiesis 50,51 . Our results showed that Tubastatin A does not affect platelet number significantly, which indicates that selective inhibition of HDAC6 might have different effect on hematopoietic stem/progenitor cells, compared to nonselective HDACIs.…”

Section: Discussionmentioning

confidence: 99%

Selective Inhibition of Histone Deacetylase-6 Alters the Composition of Circulating Blood Cells in a Lethal Septic Model

Zhao

Liu

et al. 2014

Journal of Surgical Research

View full text Add to dashboard Cite

Background-Phagocytes, especially monocytes, macrophages and dendritic cells, play a pivotal role in the innate as well as adaptive immune responses during sepsis. We have shown that inhibition of histone deacetylase (HDAC)-6 improves survival and increases bacterial clearance in a mouse model of cecal ligation and puncture (CLP). The aim of this study was to determine whether this effect was associated with changes in the number and composition of different blood cell types in the circulation.

show abstract

“…10 Treatment of primary human progenitors with HDAC inhibitors strongly promotes erythroid lineage commitment and allows for erythroid differentiation in the absence of erythropoietin. 25,26 In addition, signaling elements upstream of PKD, PLC-␥1, and PKC-⑀ are activated by erythropoietin and have been implicated in erythropoietic regulation. 31,32 PLC-␥1 null mice display embryonic lethality at day 9.5-10.5 of development with complete absence of erythroid progenitors but no deficit of granulocyte or monocyte progenitors.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggest that erythropoietin signaling may cooperate with GATA1 activation through HDAC inhibition, extending previous observations in which HDAC inhibitors promoted erythropoietin-independent erythroid maturation of human progenitors. 25,26 PKD directly phosphorylates class IIa HDACs on conserved serine residues; the phosphorylated HDACs then undergo dissociation from transcriptional complexes, promoting derepression of target genes. 8,9 Class IIa HDACs expressed in G1ER cells and human erythroid progenitors included HDAC4 and HDAC5, the former cytosolic and the latter nuclear ( Figure 3F-G).…”

Section: Involvement Of Hdac5 In Erythropoietin Cooperation With Gata1mentioning

confidence: 99%

Protein kinase D-HDAC5 signaling regulates erythropoiesis and contributes to erythropoietin cross-talk with GATA1

Delehanty

Bullock

Goldfarb

2012

Blood

View full text Add to dashboard Cite

In red cell development, the differentiation program directed by the transcriptional regulator GATA1 requires signaling by the cytokine erythropoietin, but the mechanistic basis for this signaling requirement has remained unknown. Here we show that erythropoietin regulates GATA1 through protein kinase D activation, promoting histone deacetylase 5 (HDAC5) dissociation from GATA1, and subsequent GATA1 acetylation. Mice deficient for HDAC5 show resistance to anemic challenge and altered marrow responsiveness to erythropoietin injections. In ex vivo studies, HDAC5 ؊/؊ progenitors display enhanced entry into and passage through the erythroid lineage, as well as evidence of erythropoietin-independent differentiation. These results reveal a molecular pathway that contributes to cytokine regulation of hematopoietic differentiation and offer a potential mechanism for fine tuning of lineage-restricted transcription factors by lineage-specific cytokines. ( IntroductionErythropoiesis provides a well-defined paradigm for dissecting the roles of extrinsic and intrinsic influences in hematopoietic differentiation. Erythropoietin signaling via its receptor, EpoR, and transcriptional control by the master regulator GATA1 are both required for proper red cell development in vitro and in vivo. 1 The cooperative relationship between erythropoietin signal transduction and GATA1 programming of erythropoiesis was first established by Gregory et al using progenitors expressing a conditional GATA1 mutant. 2 In the presence of erythropoietin, GATA1 activation potently induced erythroid differentiation, but in the absence of erythropoietin GATA1 activation caused extensive cell death with minimal erythroid differentiation. The molecular basis for this cooperative interaction has been intensively studied as it potentially elucidates a mechanism for extrinsic signaling exerting regulatory control over "intrinsic" transcriptional machinery.Candidate pathways for erythropoietin regulation of differentiation have involved either GATA1 phosphorylation by AKT or GATA1 stabilization by HSP70. [3][4][5] With regard to the former pathway, 2 groups identified serine 310 on GATA1 as a target of AKT phosphorylation downstream of erythropoietin activation of PI3K. 3,4 Intriguingly, transfection of constitutively active AKT eliminated requirements for either erythropoietin or JAK2 signaling in erythroid differentiation. 4,6 However, the GATA1 S310A mutant retained the capacity to program erythropoiesis in vitro, 3,4 and knock-in mice expressing GATA1 S310A showed no abnormalities in steady-state or stress erythropoiesis. 7 Therefore, the significance of erythropoietin-induced GATA1 phosphorylation remains to be determined. In the latter pathway, human erythroid progenitors subjected to erythropoietin-starvation displayed HSP70 dissociation from GATA1 and nuclear export, exposing GATA1 to caspase-mediated cleavage. 5 Whether subcellular localization of HSP70 reflects a specific erythropoietin signaling mechanism or simply levels of cellular stress is un...

show abstract

Pleiotropic role of histone deacetylases in the regulation of human adult erythropoiesis

Cited by 26 publications

References 50 publications

Histone deacetylase 2 is required for chromatin condensation and subsequent enucleation of cultured mouse fetal erythroblasts

Histone deacetylase 2 is required for chromatin condensation and subsequent enucleation of cultured mouse fetal erythroblasts

Selective Inhibition of Histone Deacetylase-6 Alters the Composition of Circulating Blood Cells in a Lethal Septic Model

Protein kinase D-HDAC5 signaling regulates erythropoiesis and contributes to erythropoietin cross-talk with GATA1

Contact Info

Product

Resources

About