Artículo del mes

The role of cytokines in establishing specific transcriptional programmes in innate immune cells has long been recognized. However, little is known about how these extracellular factors instruct innate immune cell epigenomes to engage specific differentiation states. Human monocytes differentiate under inflammatory conditions into effector cells with non-redundant functions, such as dendritic cells and macrophages. In this context, interleukin 4 (IL-4) and granulocyte macrophage colony-stimulating factor (GM-CSF) drive dendritic cell differentiation, whereas GM-CSF alone leads to macrophage differentiation.

Here, we investigate the role of IL-4 in directing functionally relevant dendritic-cell-specific DNA methylation changes. A comparison of DNA methylome dynamics during differentiation from human monocytes to dendritic cells and macrophages identified gene sets undergoing dendritic-cell-specific or macrophage-specific demethylation. Demethylation is TET2-dependent and is essential for acquiring proper dendritic cell and macrophage identity. Most importantly, activation of the JAK3-STAT6 pathway, downstream of IL-4, is required for the acquisition of the dendritic-cell-specific demethylation and expression signature, following STAT6 binding. A constitutively activated form of STAT6 is able to bypass IL-4 upstream signalling and instruct dendritic-cell-specific functional DNA methylation changes.

Our study is the first description of a cytokine-mediated sequence of events leading to direct gene-specific demethylation in innate immune cell differentiation.

 

¿Acabas de publicar un artículo interesante?

Manda la referencia a través de nuestro formulario.  Límite de edad 32 años. Los artículos seleccionados serán destacados como artículos del mes y participarán en el Premio Fisher Scientific, que se entregará en el congreso de la SEBBM (inscripción y alojamiento gratuitos).

Otros "Artículos del mes"

Dissecting the role of Epidermal Growth Factor Receptor catalytic activity during liver regeneration and hepatocarcinogenesis

Dissecting the role of Epidermal Growth Factor Receptor catalytic activity during liver regeneration and hepatocarcinogenesis

01-07-2016

Different data support a role for the epidermal growth factor receptor (EGFR) pathway during liver regeneration and hepatocarcinogenesis. However, important issues, such as the precise mechanisms mediating its actions and...

Leer más
Phytochrome and retrograde signalling pathways converge to antagonistically regulate a light-induced transcriptional network

Phytochrome and retrograde signalling pathways converge to antagonistically regulate a light-induced transcriptional network

01-06-2016

Plastid-to-nucleus retrograde signals emitted by dysfunctional chloroplasts impact photomorphogenic development, but the molecular link between retrograde- and photosensory-receptor signalling has remained unclear. Here, we show that the phytochrome and retrograde...

Leer más
Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming.

Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming.

01-05-2016

During the process of reprogramming to induced pluripotent stem (iPS) cells, somatic cells switch from oxidative to glycolytic metabolism, a transition associated with profound mitochondrial reorganization. Neither the importance of...

Leer más
p38γ and δ promote heart hypertrophy by targeting the mTOR-inhibitory protein DEPTOR for degradation

p38γ and δ promote heart hypertrophy by targeting the mTOR-inhibitory protein DEPTOR for degradation

01-04-2016

Disrupted organ growth leads to disease development. Hypertrophy underlies postnatal heart growth and is triggered after stress, but the molecular mechanisms involved in these processes are largely unknown. Here we...

Leer más
Loss of the proteostasis factor AIRAPL causes myeloid transformation by deregulating IGF-1 signaling

Loss of the proteostasis factor AIRAPL causes myeloid transformation by deregulating IGF-1 signaling

01-03-2016

AIRAPL (arsenite-inducible RNA-associated protein-like) is an evolutionarily conserved regulator of cellular proteostasis linked to longevity in nematodes, but its biological function in mammals is unknown. We show herein that AIRAPL-deficient...

Leer más
Infection exposure is a causal factor in B-precursor acute lymphoblastic leukemia as a result of Pax5 inherited susceptibility

Infection exposure is a causal factor in B-precursor acute lymphoblastic leukemia as a result of Pax5 inherited susceptibility

09-02-2016

Earlier in the past century, infections were regarded as the most likely cause of childhood B-cell precursor acute lymphoblastic leukemia (pB-ALL). However, there is a lack of relevant biologic evidence...

Leer más
 Structural and functional insights into Escherichia coli α2-macroglobulin endopeptidase snap-trap inhibition

Structural and functional insights into Escherichia coli α2-macroglobulin endopeptidase snap-trap inhibition

04-01-2016

The survival of commensal bacteria requires them to evade host peptidases. Gram-negative bacteria from the human gut microbiome encode a relative of the human endopeptidase inhibitor, α2-macroglobulin (α2M). Escherichia coli...

Leer más
NF-κB activation impairs somatic cell reprogramming in ageing

NF-κB activation impairs somatic cell reprogramming in ageing

01-12-2015

Ageing constitutes a critical impediment to somatic cell reprogramming. We have explored the regulatory mechanisms that constitute age-associated barriers, through derivation of induced pluripotent stem cells (iPSCs) from individuals with...

Leer más

miR-58 family and TGF-β pathways regulate each other in Caenorhabditis elegans

03-11-2015

Despite the fact that microRNAs (miRNAs) modulate the expression of around 60% of protein-coding genes, it is often hard to elucidate their precise role and target genes. Studying miRNA families...

Leer más
 AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest

AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest

01-10-2015

Blocking mitotic progression has been proposed as an attractive therapeutic strategy to impair proliferation of tumour cells. However, how cells survive during prolonged mitotic arrest is not well understood. We...

Leer más

Socios Protectores