A Shared Runx1-bound Zbtb16 Enhancer Directs Innate and Innate-Like Lymphoid Lineage Development
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE98662 | GEO | 2017/07/27
SECONDARY ACCESSION(S): PRJNA385830
REPOSITORIES: GEO
Similar Datasets
Project description: Not available
| S-EPMC5643357 | biostudies-literature
Project description:Natural killer (NKT) T cells exhibit tissue distribution, surface phenotype, and functional responses that are strikingly different from those of conventional T cells. The transcription factor PLZF is responsible for most of these properties, as its ectopic expression in conventional T cells is sufficient to confer to them an NKT-like phenotype. The molecular program downstream of PLZF, however, is largely unexplored. Here we report that PLZF regulates the expression of a surprisingly small set of genes, many with known immune functions. This includes several established components of the NKT cell developmental program. Transcriptional program downstream of PLZF in gammadelta NKT cells was analyzed by comparing wt, heterozygous and PLZF-deficient gammadelta NKT cells
2012-11-09 | E-GEOD-42168 | biostudies-arrayexpress
Project description:Lymphoid tissue inducer (LTi) cells are regarded as a subset of innate lymphoid cells (ILCs). However, these cells are not derived from the ILC common progenitor, which generates other ILC subsets and is defined by the expression of the transcription factor PLZF. Here we examined transcription factor(s) determining the fate of LTi progenitor versus non-LTi ILC progenitor. Conditional deletion of Gata3 resulted in the loss of PLZF+ non-LTi progenitors but not the LTi progenitors that expressed the transcription factor RORγt. Consistently, PLZF+ non-LTi progenitors expressed high amounts of GATA3 whereas GATA3 expression was low in RORγt+ LTi progenitors. The generation of both progenitors required the transcriptional regulator Id2, which defines the common helper-like innate lymphoid progenitor, but not cytokine signaling. Nevertheless, low GATA3 expression was necessary for the generation of functionally mature LTi cells. Thus, differential expression of GATA3 determines the fates and functions of distinct ILC progenitors.
2019-12-24 | GSE93863 | GEO
Project description:The transcription factor PLZF (promyelocytic leukemia zinc finger) is encoded by the BTB domain-containing 16 (Zbtb16) gene. Its repressor function regulates specific transcriptional programs. During the development of invariant natural killer T (NKT) cells, PLZF is expressed and directs their effector program but the detailed mechanisms underlying PLZF regulation of multi-stage NKT cell developmental program are not well understood. This study investigated the role of acetylation-induced PLZF activation on NKT cell development by analyzing mice expressing a mutant form of PLZF mimicking constitutive acetylation (PLZFON mice). NKT populations in PLZFON mice were reduced in proportion and numbers of cells, and the cells present were blocked at the transition from developmental stage 1 to stage 2. NKT cell subset differentiation was also altered, with T-bet+ NKT1 and RORt+ NKT17 subsets dramatically reduced, and the emergence of a T-bet-RORt- NKT cell subset with features of cells in early developmental stages rather than mature NKT2 cells. Preliminary analysis of DNA methylation patterns suggested that activated PLZF acts on the DNA methylation signature to regulate NKT cells’ entry into the early stages of development, while repressing maturation. In wild-type NKT cells, deacetylation of PLZF is possible, allowing subsequent NKT cell differentiation. Interestingly, development of other innate lymphoid and myeloid cells, that are dependent on PLZF for their generation, is not altered in PLZFON mice highlighting lineage specific regulation. Overall, we propose that specific epigenetic control of PLZF through acetylation levels is required to regulate normal NKT cell differentiation. Key points: Constitutive acetylation of PLZF (PLZFON) blocks NKT cell development. PLZFON might act on the DNA methylation signature to control gene expression. PLZF acetylation levels regulate normal NKT cell differentiation.
2021-05-24 | GSE128558 | GEO
Project description:The transcription factor PLZF (promyelocytic leukemia zinc finger) is encoded by the BTB 42 domain-containing 16 (Zbtb16) gene. Its repressor function regulates specific transcriptional 43 programs. During the development of invariant natural killer T (NKT) cells, PLZF is 44 expressed and directs their effector program but the detailed mechanisms underlying PLZF 45 regulation of multi-stage NKT cell developmental program are not well understood. This 46 study investigated the role of acetylation-induced PLZF activation on NKT cell development 47 by analyzing mice expressing a mutant form of PLZF mimicking constitutive acetylation (PLZFON mice). NKT populations in PLZFON 48 mice were reduced in proportion and numbers 49 of cells, and the cells present were blocked at the transition from developmental stage 1 to stage 2. NKT cell subset differentiation was also altered, with T-bet+ NKT1 and RORJt + 50 NKT17 subsets dramatically reduced, and the emergence of a T-bet - RORJt - 51 NKT cell subset 52 with features of cells in early developmental stages rather than mature NKT2 cells. Analysis 53 of DNA methylation patterns indicated that activated PLZF establishes a unique DNA 54 methylation signature to regulate NKT cells’ entry into the early stages of development, while 55 repressing maturation. In wild-type NKT cells, deacetylation of PLZF alleviates this 56 repression and allows subsequent NKT cell differentiation. Interestingly, development of 57 other innate lymphoid and myeloid cells, that are dependent on PLZF for their generation, is not altered in PLZFON 58 mice highlighting lineage specific regulation. Overall, we propose that 59 specific epigenetic control of PLZF through acetylation levels is required to regulate normal 60 NKT cell differentiation.
2021-04-21 | GSE171984 | GEO
Project description:Innate lymphoid cells (ILCs) are recently identified lymphocytes that limit infection and promote tissue repair at mucosal surfaces. However, the pathways underlying ILC development remain unclear. Here we show that the transcription factor NFIL3 directs the development of a committed bone marrow precursor that differentiates into all known ILC lineages. NFIL3 was required in the common lymphoid progenitor (CLP), and was essential for the differentiation of CLP, a bone marrow cell population that gives rise to all known ILC lineages. Clonal differentiation studies revealed that CXCR6+ cells within the CLP population differentiate into all ILC lineages but not T- and B-cells. We further show that NFIL3 governs ILC development by directly regulating expression of the transcription factor TOX. These findings establish that NFIL3 directs the differentiation of a committed ILC precursor that gives rise to all ILC lineages and provide insight into the defining role of NFIL3 in ILC development. This experiment is to compare gene expression profiles between wild-type and Nfil3-/- common lymphoid progenitor (CLP) cells to identify genes regulated by NFIL3. There are 6 samples in this experiment, including 3 biological replicates for wild-type CLPs and 3 biological replicates for Nfil3-/- CLPs. All mice used are on the C57BL/6 background.
2014-10-16 | E-GEOD-62337 | biostudies-arrayexpress
Project description:To identify genes that require PLZF for their regulation in NKT cells, we compared the developmental stages of thymic NKT cells from wildtype and PLZF-deficient mice The transcription factor PLZF is induced during the development of innate and innate-like lymphocytes to direct their acquisition of a T helper effector program, but the molecular mechanisms involved are poorly understood. Using biotinylation-based ChIP-seq and microarray analysis of both NKT and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program: first, PLZF bound and regulated genes encoding cytokine receptors as well as homing and adhesion receptors; second, PLZF bound and activated T helper-specific transcription factor genes that in turn control T helper specific programs; finally, PLZF bound and suppressed the transcription of Bach2, a potent general repressor of effector differentiation in naive T cells. These findings reveal the architecture of the transcriptional program recruited by PLZF and elucidate how a single transcription factor can drive the developmental acquisition of a broad effector program.
2016-05-24 | GSE81771 | GEO
Project description:Using biotinylation-based ChIP-seq and microarray analysis of both NKT and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program. The transcription factor PLZF is induced during the development of innate and innate-like lymphocytes to direct their acquisition of a T helper effector program, but the molecular mechanisms involved are poorly understood. Using biotinylation-based ChIP-seq and microarray analysis of both NKT and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program: first, PLZF bound and regulated genes encoding cytokine receptors as well as homing and adhesion receptors; second, PLZF bound and activated T helper-specific transcription factor genes that in turn control T helper specific programs; finally, PLZF bound and suppressed the transcription of Bach2, a potent general repressor of effector differentiation in naive T cells. These findings reveal the architecture of the transcriptional program recruited by PLZF and elucidate how a single transcription factor can drive the developmental acquisition of a broad effector program.
2016-05-24 | GSE81769 | GEO
Project description:Using biotinylation-based ChIP-seq and microarray analysis of both NKT and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program. The transcription factor PLZF is induced during the development of innate and innate-like lymphocytes to direct their acquisition of a T helper effector program, but the molecular mechanisms involved are poorly understood. Using biotinylation-based ChIP-seq and microarray analysis of both NKT and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program: first, PLZF bound and regulated genes encoding cytokine receptors as well as homing and adhesion receptors; second, PLZF bound and activated T helper-specific transcription factor genes that in turn control T helper specific programs; finally, PLZF bound and suppressed the transcription of Bach2, a potent general repressor of effector differentiation in naive T cells. These findings reveal the architecture of the transcriptional program recruited by PLZF and elucidate how a single transcription factor can drive the developmental acquisition of a broad effector program.
2016-05-24 | GSE81768 | GEO
Project description:Natural killer (NKT) T cells exhibit tissue distribution, surface phenotype, and functional responses that are strikingly different from those of conventional T cells. The transcription factor PLZF is responsible for most of these properties, as its ectopic expression in conventional T cells is sufficient to confer to them an NKT-like phenotype. The molecular program downstream of PLZF, however, is largely unexplored. Here we report that PLZF regulates the expression of a surprisingly small set of genes, many with known immune functions. This includes several established components of the NKT cell developmental program.
2012-11-09 | GSE42168 | GEO