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Article ; Online: Dr. Terri Grodzicker: leading

Smale, Stephen T

2023 Volume 37, Issue 1-2, Page(s) 47–49

Language	English
Publishing date	2023-04-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.350466.123
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Article ; Online: Allogeneic hematopoietic stem cell transplantation: lessons learned by a molecular immunologist/transplant patient.

Smale, Stephen T

Trends in immunology

2022 Volume 43, Issue 6, Page(s) 459–465

Abstract: Much has been learned about the genes and pathways that contribute to a diverse array of hematopoietic malignancies and other hematopoietic diseases. However, for many of these diseases, an allogeneic hematopoietic stem cell (HSC) transplant remains the ... ...

Abstract	Much has been learned about the genes and pathways that contribute to a diverse array of hematopoietic malignancies and other hematopoietic diseases. However, for many of these diseases, an allogeneic hematopoietic stem cell (HSC) transplant remains the preferred treatment option. This opinion article provides the perspective of a molecular immunologist who became a transplant patient after many years studying basic mechanisms of blood cell development. Among many lessons learned were the magnitude of racial and ethnic disparities in donor registries, the substantial improvement in outcomes over time that were due to the collective impact of numerous advances, the benefits and limitations of genetic and clinical data, and the remarkably intricate balance between promoting graft-versus-disease activity of donor cells while suppressing graft-versus-host disease (GVHD).
MeSH term(s)	Graft vs Host Disease/genetics ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans ; Transplantation Conditioning ; Transplantation, Homologous
Language	English
Publishing date	2022-04-28
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2022.03.010
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Article ; Online: Cold Spring Harbor Laboratory 2022: emerging insights and viewpoints in immunology.

Kagan, Jonathan C / Rothenberg, Ellen V / Weiss, Arthur / Rudensky, Alexander Y / Smale, Stephen T

Trends in immunology

2023 Volume 44, Issue 4, Page(s) 248–255

Abstract: Some of the current and former organizers of the Cold Spring Harbor Laboratory (CSHL) 'Gene Expression and Signaling in the Immune System' (GESIS) meeting offer opinions on emerging questions in immunology, discussing the strong value of this recurring ... ...

Abstract	Some of the current and former organizers of the Cold Spring Harbor Laboratory (CSHL) 'Gene Expression and Signaling in the Immune System' (GESIS) meeting offer opinions on emerging questions in immunology, discussing the strong value of this recurring scientific meeting in the field.
MeSH term(s)	Humans ; Immune System ; Signal Transduction
Language	English
Publishing date	2023-03-11
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2023.02.003
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Article ; Online: Transcriptional regulation in the immune system: a status report.

Smale, Stephen T

Trends in immunology

2014 Volume 35, Issue 5, Page(s) 190–194

Abstract: Regulated changes in transcription play a central role in virtually all events that accompany the development of the immune system and its response to microbial and environmental cues. Over the past 30 years, a large number of proteins that regulate ... ...

Abstract	Regulated changes in transcription play a central role in virtually all events that accompany the development of the immune system and its response to microbial and environmental cues. Over the past 30 years, a large number of proteins that regulate transcription in the immune system have been discovered and much has been learned about their mechanisms of action. However, the field remains in its infancy, with technical challenges and the complexity of gene regulation circuitry limiting our current knowledge and providing formidable barriers to further advancement. Despite these barriers, the development of new and increasingly sophisticated technologies is speeding progress towards an understanding of the gene-specific and global logic through which transcription is regulated in key immunological settings.
MeSH term(s)	Gene Expression Regulation ; Humans ; Immune System/physiology ; Immunity/genetics ; Transcription Factors/metabolism ; Transcription, Genetic
Chemical Substances	Transcription Factors
Language	English
Publishing date	2014-04-02
Publishing country	England
Document type	Letter
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2014.03.003
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Article ; Online: Species-Specific Relationships between DNA and Chromatin Properties of CpG Islands in Embryonic Stem Cells and Differentiated Cells.

Langerman, Justin / Lopez, David / Pellegrini, Matteo / Smale, Stephen T

Stem cell reports

2021 Volume 16, Issue 4, Page(s) 899–912

Abstract: CpG islands often exhibit low DNA methylation, high histone H3 lysine 4 trimethylation, low nucleosome density, and high DNase I hypersensitivity, yet the rules by which CpG islands are sensed remain poorly understood. In this study, we first evaluated ... ...

Abstract	CpG islands often exhibit low DNA methylation, high histone H3 lysine 4 trimethylation, low nucleosome density, and high DNase I hypersensitivity, yet the rules by which CpG islands are sensed remain poorly understood. In this study, we first evaluated the relationships between the DNA and the chromatin properties of CpG islands in embryonic stem cells using modified bacterial artificial chromosomes. Then, using a bioinformatic approach, we identified strict CpG-island density and length thresholds in mouse embryonic stem and differentiated cells that consistently specify low DNA methylation levels. Surprisingly, the human genome exhibited a dramatically different relationship between DNA properties and DNA methylation levels of CpG islands. Further analysis allowed speculation that this difference is accommodated in part by evolutionary changes in the nucleotide composition of orthologous promoters. Thus, a change in the rules by which CpG-island properties are sensed may have co-evolved with compensatory genome adaptation events during mammalian evolution.
MeSH term(s)	Animals ; Cell Differentiation/genetics ; Chromatin/metabolism ; CpG Islands/genetics ; DNA/metabolism ; DNA Methylation/genetics ; Embryonic Development/genetics ; Genome, Human ; Humans ; Mice ; Models, Biological ; Mouse Embryonic Stem Cells/cytology ; Mouse Embryonic Stem Cells/metabolism ; Nucleotides/genetics ; Promoter Regions, Genetic ; Species Specificity
Chemical Substances	Chromatin ; Nucleotides ; DNA (9007-49-2)
Language	English
Publishing date	2021-03-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2021.02.016
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Article ; Online: Oct4:Sox2 binding is essential for establishing but not maintaining active and silent states of dynamically regulated genes in pluripotent cells.

Lo, Jerry Hung-Hao / Edwards, Miguel / Langerman, Justin / Sridharan, Rupa / Plath, Kathrin / Smale, Stephen T

Genes & development

2022 Volume 36, Issue 19-20, Page(s) 1079–1095

Abstract: Much has been learned about the mechanisms of action of pluripotency factors Oct4 and Sox2. However, as with other regulators of cell identity, little is known about the impact of disrupting their binding motifs in a native environment or the ... ...

Abstract	Much has been learned about the mechanisms of action of pluripotency factors Oct4 and Sox2. However, as with other regulators of cell identity, little is known about the impact of disrupting their binding motifs in a native environment or the characteristics of genes they regulate. By quantitatively examining dynamic ranges of gene expression instead of focusing on conventional measures of differential expression, we found that Oct4 and Sox2 enhancer binding is strongly enriched near genes subject to large dynamic ranges of expression among cell types, with binding sites near these genes usually within superenhancers. Mutagenesis of representative Oct4:Sox2 motifs near such active, dynamically regulated genes revealed critical roles in transcriptional activation during reprogramming, with more limited roles in transcriptional maintenance in the pluripotent state. Furthermore, representative motifs near silent genes were critical for establishing but not maintaining the fully silent state, while genes whose transcript levels varied by smaller magnitudes among cell types were unaffected by nearby Oct4:Sox2 motifs. These results suggest that Oct4 and Sox2 directly establish both active and silent transcriptional states in pluripotent cells at a large number of genes subject to dynamic regulation during mammalian development, but are less important than expected for maintaining transcriptional states.
MeSH term(s)	Animals ; Transcriptional Activation ; Binding Sites ; Learning ; Mutagenesis ; Mammals
Language	English
Publishing date	2022-11-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.350113.122
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Article ; Online: The transcription factor NF-κB orchestrates nucleosome remodeling during the primary response to Toll-like receptor 4 signaling.

Feng, An-Chieh / Thomas, Brandon J / Purbey, Prabhat K / de Melo, Filipe Menegatti / Liu, Xin / Daly, Allison E / Sun, Fei / Lo, Jerry Hung-Hao / Cheng, Lijing / Carey, Michael F / Scumpia, Philip O / Smale, Stephen T

Immunity

2024 Volume 57, Issue 3, Page(s) 462–477.e9

Abstract: Inducible nucleosome remodeling at hundreds of latent enhancers and several promoters shapes the transcriptional response to Toll-like receptor 4 (TLR4) signaling in macrophages. We aimed to define the identities of the transcription factors that promote ...

Abstract	Inducible nucleosome remodeling at hundreds of latent enhancers and several promoters shapes the transcriptional response to Toll-like receptor 4 (TLR4) signaling in macrophages. We aimed to define the identities of the transcription factors that promote TLR-induced remodeling. An analysis strategy based on ATAC-seq and single-cell ATAC-seq that enriched for genomic regions most likely to undergo remodeling revealed that the transcription factor nuclear factor κB (NF-κB) bound to all high-confidence peaks marking remodeling during the primary response to the TLR4 ligand, lipid A. Deletion of NF-κB subunits RelA and c-Rel resulted in the loss of remodeling at high-confidence ATAC-seq peaks, and CRISPR-Cas9 mutagenesis of NF-κB-binding motifs impaired remodeling. Remodeling selectivity at defined regions was conferred by collaboration with other inducible factors, including IRF3- and MAP-kinase-induced factors. Thus, NF-κB is unique among TLR4-activated transcription factors in its broad contribution to inducible nucleosome remodeling, alongside its ability to activate poised enhancers and promoters assembled into open chromatin.
MeSH term(s)	NF-kappa B/metabolism ; Toll-Like Receptor 4/genetics ; Toll-Like Receptor 4/metabolism ; Nucleosomes ; Signal Transduction ; Gene Expression Regulation ; Transcription Factor RelA/metabolism
Chemical Substances	NF-kappa B ; Toll-Like Receptor 4 ; Nucleosomes ; Transcription Factor RelA
Language	English
Publishing date	2024-03-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2024.02.004
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Article ; Online: The Ly6C(lo)-Down: Targeting Developmental Enhancers for Cell Subset Depletion.

Thomas, Brandon J / Smale, Stephen T

Immunity

2016 Volume 45, Issue 5, Page(s) 949–951

Abstract: The diversity of mononuclear phagocytes has made it difficult to ascribe cellular functions to sub-populations using conventional loss-of-function approaches. In this issue of Immunity, Thomas et al. (2016) highlight the value of excising enhancer ... ...

Abstract	The diversity of mononuclear phagocytes has made it difficult to ascribe cellular functions to sub-populations using conventional loss-of-function approaches. In this issue of Immunity, Thomas et al. (2016) highlight the value of excising enhancer domains, effectively depleting defined lineages without altering other cellular physiology.
MeSH term(s)	Humans ; Monocytes/immunology ; Regulatory Sequences, Nucleic Acid
Language	English
Publishing date	2016--15
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2016.10.034
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Article ; Online: IL-10 constrains sphingolipid metabolism to limit inflammation.

York, Autumn G / Skadow, Mathias H / Oh, Joonseok / Qu, Rihao / Zhou, Quan D / Hsieh, Wei-Yuan / Mowel, Walter K / Brewer, J Richard / Kaffe, Eleanna / Williams, Kevin J / Kluger, Yuval / Smale, Stephen T / Crawford, Jason M / Bensinger, Steven J / Flavell, Richard A

Nature

2024 Volume 627, Issue 8004, Page(s) 628–635

Abstract: Interleukin-10 (IL-10) is a key anti-inflammatory cytokine that can limit immune cell activation and cytokine production in innate immune cell ... ...

Abstract	Interleukin-10 (IL-10) is a key anti-inflammatory cytokine that can limit immune cell activation and cytokine production in innate immune cell types
MeSH term(s)	Animals ; Humans ; Mice ; Ceramides/chemistry ; Ceramides/metabolism ; Fatty Acids, Unsaturated/biosynthesis ; Fatty Acids, Unsaturated/metabolism ; Homeostasis ; Immunity, Innate ; Inflammation/genetics ; Inflammation/metabolism ; Inflammation/pathology ; Interleukin-10/deficiency ; Interleukin-10/genetics ; Interleukin-10/metabolism ; Proto-Oncogene Proteins c-rel ; Sphingolipids/metabolism
Chemical Substances	Ceramides ; CERS2 protein, human (EC 2.3.1.24) ; Cers2 protein, mouse (EC 2.3.1.24) ; Fatty Acids, Unsaturated ; Interleukin-10 (130068-27-8) ; Proto-Oncogene Proteins c-rel ; REL protein, human ; Sphingolipids
Language	English
Publishing date	2024-02-21
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-024-07098-5
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Article ; Online: Transcriptional regulation in the innate immune system.

Smale, Stephen T

Current opinion in immunology

2012 Volume 24, Issue 1, Page(s) 51–57

Abstract: In cells of the innate immune system, the transcriptional response to a microbial stimulus is tailored to both the stimulus and cell type, suggesting the existence of highly sophisticated regulatory mechanisms. Early studies suggested that specificity is ...

Abstract	In cells of the innate immune system, the transcriptional response to a microbial stimulus is tailored to both the stimulus and cell type, suggesting the existence of highly sophisticated regulatory mechanisms. Early studies suggested that specificity is dictated by sets of differentially induced transcription factors that synergistically activate target genes containing their binding sites. However, recent studies have revealed additional interrelated regulatory layers, which are the topic of this article. In particular, individual transcription factors may require different post-translational modifications and coregulatory interactions to regulate different target genes. Furthermore, competence for induction is programmed at an early stage of development by factors involved in lineage commitment, and the architecture and chromatin structure of each promoter play critical roles in transcriptional specificity.
MeSH term(s)	Animals ; Bacterial Infections/genetics ; Gene Expression Regulation/physiology ; Humans ; Immunity, Innate/genetics ; Transcription Factors/physiology ; Transcription, Genetic
Chemical Substances	Transcription Factors
Language	English
Publishing date	2012-01-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2011.12.008
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