Direct targets of pStat5 signalling in erythropoiesis

Gillinder, Kevin R., Tuckey, Hugh, Bell, Charles C., Magor, Graham W., Huang, Stephen, Ilsley, Melissa D. and Perkins, Andrew C. (2017) Direct targets of pStat5 signalling in erythropoiesis. PLoS One, 12 7: 1191-1192. doi:10.1371/journal.pone.0180922


Author Gillinder, Kevin R.
Tuckey, Hugh
Bell, Charles C.
Magor, Graham W.
Huang, Stephen
Ilsley, Melissa D.
Perkins, Andrew C.
Title Direct targets of pStat5 signalling in erythropoiesis
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2017-07-21
Year available 2017
Sub-type Article (original research)
DOI 10.1371/journal.pone.0180922
Open Access Status DOI
Volume 12
Issue 7
Start page 1191
End page 1192
Total pages 20
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Language eng
Abstract The plant hormone strigolactone (SL) is important for many processes in plants, but its molecular mode of action has been difficult to elucidate. A new discovery has identified the SPL transcription factor, IPA1, as a crucial component directly involved in SL signaling.
Formatted abstract
Erythropoietin (EPO) acts through the dimeric erythropoietin receptor to stimulate proliferation, survival, differentiation and enucleation of erythroid progenitor cells. We undertook two complimentary approaches to find EPO-dependent pSTAT5 target genes in murine erythroid cells: RNA-seq of newly transcribed (4sU-labelled) RNA, and ChIP-seq for pSTAT5 30 minutes after EPO stimulation. We found 302 pSTAT5-occupied sites: ~15% of these reside in promoters while the rest reside within intronic enhancers or intergenic regions, some >100kb from the nearest TSS. The majority of pSTAT5 peaks contain a central palindromic GAS element, TTCYXRGAA. There was significant enrichment for GATA motifs and CACCC-box motifs within the neighbourhood of pSTAT5-bound peaks, and GATA1 and/or KLF1 co-occupancy at many sites. Using 4sU-RNA-seq we determined the EPO-induced transcriptome and validated differentially expressed genes using dynamic CAGE data and qRT-PCR. We identified known direct pSTAT5 target genes such as Bcl2l1, Pim1 and Cish, and many new targets likely to be involved in driving erythroid cell differentiation including those involved in mRNA splicing (Rbm25), epigenetic regulation (Suv420h2), and EpoR turnover (Clint1/EpsinR). Some of these new EpoR-JAK2-pSTAT5 target genes could be used as biomarkers for monitoring disease activity in polycythaemia vera, and for monitoring responses to JAK inhibitors.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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