Roles and regulations of the ETS transcription factor ELF4/MEF

Suico, Mary Ann; Shuto, Tsuyoshi; Kai, Hirofumi

doi:10.1093/jmcb/mjw051

Cited by 48 publications

(50 citation statements)

References 77 publications

(129 reference statements)

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“…We chose to focus on TFs identified at an early stage of differentiation (4h), as they are likely to be initiators of the transcriptional response to ATRA, rather than secondary or tertiary changes 20 . Among the up-regulated TFs, IRF1 and ELF4 regulate expression of genes involved in immune responses, proliferation and/or apoptosis p53 52,53 . In particular, IRF1 is involved in normal granulocytic maturation as well as expression of other crucial regulators of granulocytic differentiation such as CEBPα, ε, and PU.1 54,55 .…”

Section: Discussionmentioning

confidence: 99%

Identification of drugs for leukaemia differentiation therapy by network pharmacology

et al. 2019

Preprint

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Acute leukaemias differ from their normal haematopoietic counterparts in their inability to differentiate. This phenomenon is thought to be the result of aberrant cellular reprogramming involving transcription factors (TFs). Here we leveraged on Mogrify, a network-based algorithm, to identify TFs and their gene regulatory networks that drive differentiation of the acute promyelocytic leukaemia (APL) cell line NB4 in response to ATRA (all-trans retinoic acid). We further integrated the detected TF regulatory networks with the Connectivity Map (CMAP) repository and recovered small molecule drugs which induce similar transcriptional changes. Our method outperformed standard approaches, retrieving ATRA as the top hit. Of the other drug hits, dimaprit and mebendazole enhanced ATRA-mediated differentiation in both parental NB4 and ATRA-resistant NB4-MR2 cells. Thus, we provide proof-of-principle of our network-based computational platform for drug discovery and repositioning in leukaemia differentiation therapy, which can be extended to other dysregulated disease states.

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Section: Discussionmentioning

confidence: 99%

Identification of drugs for leukaemia differentiation therapy by network pharmacology

et al. 2019

Preprint

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“…Ef-ELF (ELF2) belongs to the Ets family, whose members are powerful regulators of cell proliferation, angiogenesis, hematopoiesis, tumour transformation, and differentiation 31,32 . However, the functions of ELF1, ELF2, and ELF4 in chordates are associated with lymphoid and endothelial cell differentiation, hematopoietic stem and progenitor cell survival, and tumour suppression [33][34][35][36] . Sea urchin elf expression is detected everywhere in late gastrula, being more concentrated in the gut 30 .…”

Section: Search Of the Most Likely Candidates For The Role Of Transdimentioning

confidence: 99%

The Eupentacta fraudatrix transcriptome provides insights into regulation of cell transdifferentiation

Boyko

Girich

Tkacheva

et al. 2020

Sci Rep

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the holothurian Eupentacta fraudatrix is a unique organism for studying regeneration mechanisms. Moreover, E. fraudatrix can quickly restore parts of its body and entire organ systems, yet at the moment, there is no data on the participation of stem cells in the process. to the contrary, it has been repeatedly confirmed that this process is only due to the transformation of terminally differentiated cells. in this study, we examine changes in gene expression during gut regeneration of the holothurian E. fraudatrix. transcriptomes of intestinal anlage of the three stages of regeneration, as well as the normal gut, were sequenced with an Illumina sequencer (San Diego, CA, USA). We identified 14,617 sea urchin protein homologs, of which 308 were transcription factors. After analysing the dynamics of gene expression during regeneration and the map of biological processes in which they participate, we

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“…A similar search for DNA motifs enriched in chromatin regions that become accessible specifically upon CAF-1 depletion identified a sequence recognized by the E74 Like ETS transcription factors ELF1 and ELF4 ( Figure. 4f), which are known primarily for their involvement in regulating immune responses (Gallant and Gilkeson, 2006). Elf1 in particular is more broadly expressed during hematopoiesis compared to C/EBPa (Figure4-figure supplement 2c) and has been proposed to regulate erythroid differentiation as well as development of natural killer cells and T cells (Suico et al, 2017). Markedly, we find potential Elf1 binding sites near genes upregulated only in the CAF-1 OFF condition ( Figure. 4h and Figure4-figure supplement 2g).…”

Section: Caf-1 Inhibits Multiple Transcriptional Programs To Block DImentioning

confidence: 73%

The Histone Chaperone CAF-1 Sustains Myeloid Lineage Identity

Guo¹,

Murn³

et al. 2020

Preprint

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During hematopoiesis, stem and progenitor cells become progressively restricted in their differentiation potential. This process is driven by lineage-specific transcription factors and is accompanied by dynamic changes in chromatin structure. The chromatin assembly factor complex CAF-1 is a key regulator of cellular plasticity in various cell lineages in different organisms. However, whether CAF-1 sustains lineage identity during normal homeostasis is unclear. To address this question, we investigated the role of CAF-1 in myeloid progenitor cells. CAF-1 suppression in myeloid progenitors triggered their rapid commitment but incomplete differentiation toward granulocyte, megakaryocyte, and erythrocyte lineages, resulting in a mixed cellular state. Through comparison with a canonical paradigm of directed terminal myeloid differentiation, we define changes in chromatin accessibility that underlie a unique transcriptome of the aberrantly matured CAF-1 deficient cells. We further identify C/EBPα and ELF1 as key transcription factors whose control of myeloid lineage commitment is kept in check by CAF-1. These findings shed new light on molecular underpinnings of hematopoiesis and suggest that manipulation of chromatin accessibility through modulating CAF-1 levels may provide a powerful strategy for controlled differentiation of blood cells.

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Roles and regulations of the ETS transcription factor ELF4/MEF

Cited by 48 publications

References 77 publications

Identification of drugs for leukaemia differentiation therapy by network pharmacology

Identification of drugs for leukaemia differentiation therapy by network pharmacology

The Eupentacta fraudatrix transcriptome provides insights into regulation of cell transdifferentiation

The Histone Chaperone CAF-1 Sustains Myeloid Lineage Identity

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