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Bone density loci identified by genome-wide association studies segregate a lineage-specific PU.1-dependent gene regulatory network in osteoclasts [MoEx-1_0-st array]

ABSTRACT: Eavluation of temporal expression kinetics during mouse osteoclast differentiation evaluated by microarray. We overlayed gene expression data with correspoding DNA binding data from MITF and PU.1 ChIP-seq to evaluate gene regulatory networks in osteoclasts.

ORGANISM(S): Mus musculus

PROVIDER: GSE107296 | GEO | 2018/04/10

REPOSITORIES: GEO

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Bone density loci identified by genome-wide association studies segregate a lineage-specific PU.1-dependent gene regulatory network in osteoclasts [MoEx-1_0-st array]

Project description:Bone density loci identified by genome-wide association studies segregate a lineage-specific PU.1-dependent gene regulatory network in osteoclasts [MoEx-1_0-st array]

| PRJNA419649 | ENA

Bone density loci identified by genome-wide association studies segregate a lineage-specific PU.1-dependent gene regulatory network in osteoclasts [ChIP-seq]

Project description:Genome-wide association studies (GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to the trait. In this study, by integrating publicly available lineage-specific enhancers from mesenchymal and myeloid compartments with bone mineral density loci, we were able to segregate osteoblast- and osteoclast (OC)-specific functions. Specifically, in OCs, a PU.1-dependent transcription factor (TF) network was revealed. Further we conducted functional genomic analysis PU.1 and MITF genome wide binding with corresponding gene expression analysis which revealed a TF network essential for OC differentiation. Several of these TFs were regulated by cooperative binding of PU.1 with BRD4 to form superenhancers. Further, PU.1 is essential for conformational changes in the superenhancer region of Nfatc1. In summary, our study demonstrates that utilizing GWASs with genome-wide binding studies as a filter helps to decipher lineage-specific pathways contributing to complex disease states.

2018-04-10 | GSE107294 | GEO

Effects of the long noncoding RNA Malat1 on gene expression [MoEx-1_0-st]

Project description:Malat1 is an abundant long noncoding RNA that localizes to nuclear bodies known as nuclear speckles, which contain a distinct set of pre-mRNA processing factors. Previous in vitro studies have demonstrated that Malat1 interacts with pre-mRNA splicing factors, including the serine- and arginine-rich (SR) family of proteins, and regulates a variety of biological processes, including cancer cell migration, synapse formation, cell cycle progression, and responses to serum stimulation. To address the physiological function of Malat1 in a living organism, we generated Malat1-KO (KO) mice using homologous recombination. Unexpectedly, the Malat1-KO mice were viable and fertile, showing no apparent phenotypes. Nuclear speckle markers were also correctly localized in cells that lacked Malat1. However, the cellular levels of another long noncoding RNA, Neat1, which is an architectural component of nuclear bodies known as paraspeckles, were downregulated in a particular set of tissues and cells lacking Malat1. To address if the absence of Malat1 affects the expression of other genes, including other long noncoding RNA, microarrays were used to study the impact of knocking-out Malat1 on global gene expression in hippocampal neurons.

2012-06-25 | GSE37706 | GEO

Gene expression study of blood monocytes in pre- and postmenopausal females with low or high bone mineral density (HuEx-1_0-st-v2)

2016-06-01 | GSE56814 | GEO

Multiple levels of transcriptional regulation by PLZF in NKT cell development [MoEx-1_0-st]

Project description:To identify genes that PLZF is sufficient to modulate in T cells, we compared CD4+ CD8- (CD4SP) thymocytes that overexpressed PLZF to their wildtype counterparts 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 | GSE81770 | GEO

Effects of the long noncoding RNA Malat1 on gene expression [MoEx-1_0-st]

2012-06-24 | E-GEOD-37706 | biostudies-arrayexpress

Bone density loci identified by genome-wide association studies segregate a lineage-specific PU.1-dependent gene regulatory network in osteoclasts

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-04-10 | GSE107297 | GEO

Gene expression study of blood monocytes in pre- and postmenopausal females with low or high bone mineral density (HuEx-1_0-st-v2)

Project description:Comparison of circulating monocytes from pre- and postmenopausal females with low or high bone mineral density (BMD). Circulating monocytes are progenitors of osteoclasts, and produce factors important to bone metabolism. Results provide insight into the role of monocytes in osteoporosis. We identify osteoporosis genes by microarray analyses of monocytes in high vs. low hip BMD (bone mineral density) subjects. Microarray analyses of monocytes were performed using Affymetrix 1.0 ST arrays in 73 Caucasian females (age: 47-56) with extremely high (mean ZBMD =1.38, n=42, 16 pre- and 26 postmenopausal subjects) or low hip BMD (mean ZBMD=-1.05, n=31, 15 pre- and 16 postmenopausal subjects). Differential gene expression analysis in high vs. low BMD subjects was conducted in the total cohort as well as pre- and post-menopausal subjects.

2016-06-01 | E-GEOD-56814 | biostudies-arrayexpress

Bone density loci identified by genome-wide association studies segregate a lineage-specific PU.1-dependent gene regulatory network in osteoclasts [HsMmMicroarray]

Project description:Similar temporal expression kinetics of transcription factors in human and mouse osteoclast differentiation evaluated by microarray We used the identical differentiation conditions to evaluate gene expression kinetics of mouse and human osteoclast differentiation by microarray

2018-04-10 | GSE107295 | GEO

Bone density loci identified by genome-wide association studies segregate a lineage-specific PU.1-dependent gene regulatory network in osteoclasts

Project description:Bone density loci identified by genome-wide association studies segregate a lineage-specific PU.1-dependent gene regulatory network in osteoclasts

| PRJNA419645 | ENA

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