Epigenetic program and transcription factor circuitry of dendritic cell development

Lin, Qiong; Chauvistré, Heike; Costa, Ivan G.; Gusmao, Eduardo Gade; Mitzka, Saskia; Hänzelmann, Sonja; Baying, Bianka; Klisch, Theresa; Moriggl, Richard; Hennuy, Benoît; Smeets, Hubert; Hoffmann, Kurt; Beneš, Vladimı́r; Seré, Kristin; Zenke, Martin

doi:10.1093/nar/gkv1056

Cited by 50 publications

(97 citation statements)

References 69 publications

(124 reference statements)

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“…67,79 Similar results are observed for these chromatin marks in pDCs. 56,67 These studies suggest that the chromatin landscape of TFs crucial for DC differentiation have been established prior to inflammatory stimulation and perhaps early during subset-specification stage. It is important to examine which chromatin-modifying enzyme(s) play a critical role in modifying these enhancers under steady-state and inflammatory conditions.…”

Section: Epigenetic Processes In Dcsmentioning

confidence: 92%

“…The amount of both H3K4me1 and H3K27ac in pDCs is significantly higher for pDC-specific genes than moDC-specific genes. 43,56 Similarly, moDC-specific genes demonstrated significantly higher H3K4me1 and H3K27ac intensity than pDC-specific genes. 43,56 Identification of these DC-specific enhancer regions is important for defining the specific effects of epigenetic regulators.…”

Section: Epigenetic Processes In Dcsmentioning

confidence: 96%

“…24,26,41,43 For example, HSPC-derived cDCs (CD11c + SeglecH − B220 − ) can be further classified into 2 classes: cDC1 (CD8α + /CD103 + D11b − ) and cDC2 (CD8α − CD11b + ). 24,26,56–58 cDC1 are particularly efficient in cross-presenting exogenous antigens to CD8 + CTLs. cDC1 development requires the expression of TFs, including BATF3, IRF8, and ID2.…”

Section: Transcription Factors and Generation Of Distinct DC Subsetsmentioning

confidence: 99%

“…24,26,29 Granulocyte macrophage colony-stimulating factor–driven moDC differentiation requires expression of functional IRF4 and CEBPB. 56,62,67,74 CEBPB can promote moDC differentiation by counteracting IRF8 effects. 67 Notably, KLF4 induces a set of monocyte lineage–associated molecules and is a key switch factor regulating differentiation of monocytes into moDCs.…”

Section: Transcription Factors and Generation Of Distinct DC Subsetsmentioning

confidence: 99%

“…For example, pDC and moDCs are distinguished by thousands of differential enhancers. 41,43,56 Analysis of H3K4me1 and H3K27Ac modifications reveals a large number of differential sites between pDCs and moDCs. The amount of both H3K4me1 and H3K27ac in pDCs is significantly higher for pDC-specific genes than moDC-specific genes.…”

Section: Epigenetic Processes In Dcsmentioning

confidence: 99%

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Epigenetic Regulation of Dendritic Cell Development and Function

Tian¹,

Meng²,

Zhang³

2017

Cancer J

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The immune system is characterized by the generation of structurally and functionally heterogeneous immune cells that constitute complex innate and adaptive immunity. This heterogeneity of immune cells results from changes in the expression of genes without altering DNA sequence. To achieve this heterogeneity, immune cells orchestrate the expression and functional status of transcription factor (TF) networks, which can be broadly categorized into 3 classes: pioneer TFs that facilitate initial commitment and differentiation of hematopoietic cells, subset-specific TFs that promote the generation of selected cell lineages, and immune-signaling TFs that regulate specialized function in differentiated cells. Epigenetic mechanisms are known to be critical for organizing the TF networks, thereby controlling immune cell lineage-fate decisions, plasticity, and function. The effects of epigenetic regulators can be heritable during cell mitosis, primarily through the modification of DNA and histone methylation patterns at gene loci. By doing so, the immune system is enabled to mount a selective but robust response to stimuli, such as pathogens, tumor cells, autoantigens, or allogeneic antigens in the setting of transplantation, while preserving the immune cell reservoir necessary for protecting the host against numerous other unexpected stimuli and limit detrimental effect of systemic inflammatory reactions.

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Section: Epigenetic Processes In Dcsmentioning

confidence: 92%

Section: Epigenetic Processes In Dcsmentioning

confidence: 96%

Section: Transcription Factors and Generation Of Distinct DC Subsetsmentioning

confidence: 99%

Section: Transcription Factors and Generation Of Distinct DC Subsetsmentioning

confidence: 99%

Section: Epigenetic Processes In Dcsmentioning

confidence: 99%

See 3 more Smart Citations

Epigenetic Regulation of Dendritic Cell Development and Function

Tian¹,

Meng²,

Zhang³

2017

Cancer J

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Advances in understanding epigenetic impacts on dendritic cell regulation and function

Verlander

Cummings

Brown

et al. 2022

Clinical and Translational Dis

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Dendritic cells (DCs) are the only cells empowered with inducing primary immune response among resting naïve T lymphocytes, hence it is crucial to understand the regulation and function of DCs. During an adaptive immune response, DCs acquire antigens from invasive entities and present the antigens on their own cell surface, hence they are also known as professional antigen‐presenting cells. Epigenetic modifications to the genome play an important role in both the development and the function of DCs. In this direction, significant advancements have been made using high‐throughput methods like ATAC‐seq, ChIP‐seq, RNA‐seq, bisulfite‐seq and so forth to uncover chromatin accessibility landscape, genome‐wide transcription factor (TF) binding, complete transcriptomic profiles, and DNA methylation, respectively. DCs lineage specification and function are determined by TF binding, which is dependent on epigenetic modifications. However, major gaps in knowledge still exist regarding how and why aberrant epigenetic modifications result in defective development and function of DCs leading to an impaired immune system. Hence, this review compiles up‐to‐date literature regarding the exquisite regulation of DCs via epigenetic regulation, to emphasize the potential of further epigenetics research on DCs for addressing current gaps of knowledge in the field. The review also briefly highlights recent findings on DC defects in coronavirus disease 2019 revealed by single‐cell RNA‐seq, and the importance of DCs in clinical trials. Overall, the review highlights how epigenetics‐based state‐of‐the‐art high‐throughput technology can help discoveries on DCs which are crucial to the immune system and pathogenesis, and how DCs are currently targeted for therapeutic developments and clinical trials.

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CRISPR/Cas9 editing in conditionally immortalized HoxB8 cells for studying gene regulation in mouse dendritic cells

Look

Prithiviraj

et al. 2021

Eur J Immunol

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cells r CRISPR/Cas r dCas9 r HoxB8 r gene regulation Additional supporting information may be found online in the Supporting Information section at the end of the article. Dendritic cells (DC) are regulated by intricate genetic programs, which determine DC development, subset specification, and DC functions [1,2]. Here, we provide a workflow for CRISPR/Cas9 targeting noncoding cis-regulatory elements of transcription in DC in conditionally immortalized HoxB8 multipotent hematopoietic progenitors (HoxB8 MPP). This includes (i) induced CRISPR/Cas9 editing of an IRF8 enhancer element in single-cell HoxB8 MPP and (ii) CRISPR/dCas9-mediated IRF8 promoter silencing.DC development from hematopoietic stem cells (HSC) and MPP entails sequential steps of lineage commitment and differentiation. First, HSC and MPP are committed to DC restricted common DC progenitors (CDP), which second further differentiate into specific DC subsets: antigen-presenting classical DC (cDC) type 1 and type 2 (cDC1 and cDC2, respectively) and interferon-producing plasmacytoid DC (pDC) [1][2][3]. DC differentiation involves several transcription factors and cis-acting regulatory elements that control DC fate and subset specification [1,2].

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Epigenetic program and transcription factor circuitry of dendritic cell development

Cited by 50 publications

References 69 publications

Epigenetic Regulation of Dendritic Cell Development and Function

Epigenetic Regulation of Dendritic Cell Development and Function

Advances in understanding epigenetic impacts on dendritic cell regulation and function

CRISPR/Cas9 editing in conditionally immortalized HoxB8 cells for studying gene regulation in mouse dendritic cells

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