Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

57 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Histone variant H2A.Z.2 mediates proliferation and drug sensitivity of malignant melanoma [ChIP-seq]

ABSTRACT: Here we report a novel role for H2A.Z.2 (H2AFV) as a mediator of cell proliferation and sensitivity to targeted therapies in malignant melanoma. While both H2A.Z.1 and H2A.Z.2 are highly expressed in metastatic melanoma and correlate with decreased patient survival, only H2A.Z.2 deficiency results in impaired cellular proliferation of melanoma cells, which occurs via a G1/S arrest. Integrated gene expression and ChIP-seq analyses revealed that H2A.Z.2 positively regulates E2F target genes, and that such genes acquire a distinct H2A.Z occupancy signature over the promoter and gene body in metastatic melanoma cells. We further identified the BET family member BRD2 as an H2A.Z-interacting protein in melanoma cells, and demonstrate that H2A.Z.2 silencing cooperates with BET inhibition to induce cell death. Cross-linked ChIP in SKmel147 melamoma cell line for E2F1 and BRD2

ORGANISM(S): Homo sapiens

SUBMITTER: Emily Bernstein

PROVIDER: E-GEOD-68223 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Histone variant H2A.Z.2 mediates proliferation and drug sensitivity of malignant melanoma [native ChIP-seq]

Project description:Here we report a novel role for H2A.Z.2 (H2AFV) as a mediator of cell proliferation and sensitivity to targeted therapies in malignant melanoma. While both H2A.Z.1 and H2A.Z.2 are highly expressed in metastatic melanoma and correlate with decreased patient survival, only H2A.Z.2 deficiency results in impaired cellular proliferation of melanoma cells, which occurs via a G1/S arrest. Integrated gene expression and ChIP-seq analyses revealed that H2A.Z.2 positively regulates E2F target genes, and that such genes acquire a distinct H2A.Z occupancy signature over the promoter and gene body in metastatic melanoma cells. We further identified the BET family member BRD2 as an H2A.Z-interacting protein in melanoma cells, and demonstrate that H2A.Z.2 silencing cooperates with BET inhibition to induce cell death. Mononucleosomes from SK-mel147 (wt and stably expressing eGFP-H2A. eGFP-H2A.Z.1 and eGFP-H2A.Z.2) and melanocytes were isolated for ChIP with H2A.Z antibody or GFP trap beads (Chromotek).

2015-07-01 | E-GEOD-68222 | biostudies-arrayexpress

Histone variant H2A.Z.2 mediates proliferation and drug sensitivity of malignant melanoma [RNA-seq]

Project description:Here we report a novel role for H2A.Z.2 (H2AFV) as a mediator of cell proliferation and sensitivity to targeted therapies in malignant melanoma. While both H2A.Z.1 and H2A.Z.2 are highly expressed in metastatic melanoma and correlate with decreased patient survival, only H2A.Z.2 deficiency results in impaired cellular proliferation of melanoma cells, which occurs via a G1/S arrest. Integrated gene expression and ChIP-seq analyses revealed that H2A.Z.2 positively regulates E2F target genes, and that such genes acquire a distinct H2A.Z occupancy signature over the promoter and gene body in metastatic melanoma cells. We further identified the BET family member BRD2 as an H2A.Z-interacting protein in melanoma cells, and demonstrate that H2A.Z.2 silencing cooperates with BET inhibition to induce cell death. Expression levels for non tumorigenic (Melanocytes) and human melanoma cell line SKmel147, before and after JQ1 treatement

2015-07-01 | E-GEOD-68221 | biostudies-arrayexpress

Histone variant H2A.Z.2 mediates proliferation and drug sensitivity of malignant melanoma (expression)

Project description:Here we report a novel role for H2A.Z.2 (H2AFV) as a mediator of cell proliferation and sensitivity to targeted therapies in malignant melanoma. While both H2A.Z.1 and H2A.Z.2 are highly expressed in metastatic melanoma and correlate with decreased patient survival, only H2A.Z.2 deficiency results in impaired cellular proliferation of melanoma cells, which occurs via a G1/S arrest. Integrated gene expression and ChIP-seq analyses revealed that H2A.Z.2 positively regulates E2F target genes, and that such genes acquire a distinct H2A.Z occupancy signature over the promoter and gene body in metastatic melanoma cells. We further identified the BET family member BRD2 as an H2A.Z-interacting protein in melanoma cells, and demonstrate that H2A.Z.2 silencing cooperates with BET inhibition to induce cell death. Total RNA samples from SKmel147 melanoma cell line. Transcript levels were analyzed after control or H2AZ variant RNA interference.

2015-07-01 | E-GEOD-59026 | biostudies-arrayexpress

macroH2A histone variants act as a barrier upon reprogramming towards pluripotency

Project description:Here we report that the histone variant macroH2A acts as a barrier to induced pluripotency. Using fibroblasts isolated from macroH2A double knockout mice, we observed enhanced reprogramming efficiency compared to fibroblasts from wild type animals. We further show that macroH2A isoforms act synergistically in this process. Genomic analysis in wild type fibroblasts reveals that macroH2A1 and H3K27me3 domains co-localize and occupy pluripotency genes. While the absence of macroH2A does not affect H3K27me3 in fibroblasts, macroH2A1 is highly enriched at a set of Utx target genes that are reactivated early during iPS reprogramming. Mononucleosomes from Dermal Fibroblasts (from wt and macroH2A1 and macroH2A2 double knockout mice) were isolated and ChIP'd with mH2A1, H3K27me3 and H3K27ac antibodies. DNA from Input and ChIP samples was purified and sequenced on Illumina's Hiseq.

2013-03-01 | E-GEOD-40813 | biostudies-arrayexpress

Targeting the SIN3A-PF1 Interaction inhibits Epithelial to Mesenchymal Transition and Maintenance of a Stem Cell Phenotype in Triple Negative Breast Cancer (MNase-seq)

Project description:Triple negative breast cancer (TNBC) is characterized by a poorly differentiated phenotype and limited treatment options. Aberrant epigenetics in this subtype represent a potential therapeutic opportunity, but a better understanding of the mechanisms contributing to the TNBC pathogenesis is required. The SIN3 molecular scaffold performs a critical role in multiple cellular processes, including epigenetic regulation, and has been identified as a potential therapeutic target. Using a competitive peptide corresponding to the SIN3 interaction domain of MAD (Tat-SID), we investigated the functional consequences of selectively blocking the paired amphipathic helix (PAH2) domain of SIN3. Here, we report the identification of the SID-containing adaptor PF1 as a factor required for maintenance of the TNBC stem cell phenotype and epithelial to mesenchymal transition (EMT). Tat-SID peptide blocked the interaction between SIN3A and PF1, leading to epigenetic modulation and transcriptional downregulation of TNBC stem cell and EMT markers. Importantly, Tat-SID treatment led to a reduction in primary tumor growth and disseminated metastatic disease in vivo. In support of these findings, knockdown of PF1 expression phenocopied treatment with Tat-SID both in vitro and in vivo. These results demonstrate a critical role for a complex containing SIN3A and PF1 in TNBC and provide a rational for its therapeutic targeting. Mononucleosomes from MDA-MB-231 cells were isolated and ChIP with H3K4me3 antibody. DNA from Input and ChIP samples was purified and sequenced on Illumina Hiseq.

2015-11-02 | E-GEOD-73869 | biostudies-arrayexpress

ATRX-mediated chromatin association of histone variant macroH2A1 regulates alpha globin gene expression

Project description:The histone variant macroH2A generally associates with transcriptionally inert chromatin, however the factors that regulate its chromatin incorporation remain elusive. Here, we identify the SWI/SNF helicase, ATRX, as a novel macroH2A interacting protein. Unlike its role in assisting H3.3 chromatin deposition, ATRX acts as a negative regulator of macroH2A’s chromatin association. In human erythroleukemic cells deficient for ATRX, ChIP-sequencing studies reveal that macroH2A accumulates at the HBA gene cluster on the subtelomere of chromosome 16, coinciding with the loss of α globin expression. Collectively, our results implicate deregulation of macroH2A’s distribution as a contributing factor to the α thalassemia phenotype of ATRX syndrome. Mononucleosomes from K562 cells bearing integrated lentiviral shRNA constructs targeting either luciferase (shluc) or ATRX (sh92) were isolated and ChIP'd with mH2A1 antibody. DNA from shluc Input and the two mH2A1 ChIPs were isolated and sequenced on Illumina's Hiseq.

2012-03-08 | E-GEOD-35339 | biostudies-arrayexpress

Targeting the SIN3A-PF1 Interaction inhibits Epithelial to Mesenchymal Transition and Maintenance of a Stem Cell Phenotype in Triple Negative Breast Cancer

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-11-02 | E-GEOD-73871 | biostudies-arrayexpress

The chromatin remodeler ATRX binds to atypical chromatin domains at the 3â exons of ZNF genes to preserve H3K9me3 enrichment

Project description:Here, we report that ATRX co-localizes with the H3K9-methyl transferase SETDB1 (also known as ESET), the co-repressor TRIM28 (also known as KAP1), and the transcription factor ZNF274 at 3â exons of Zinc Finger Genes (ZNFs) containing an atypical H3K9me3/H3K36me3 chromatin signature. Disruption of ATRX and ZNF274 leads to a significant reduction of H3K9me3, particularly at the 3â ZNF exons and other atypical chromatin regions, higher percentages of DNA damage, and defects in cell cycle. Taken together, our studies suggest that ATRX binds the 3â exons of ZNFs to maintain genomic stability through the regulation of their H3K9me3 levels XL-MNase ChIP-seq of ATRX was performed in the erythroleukemic cell line K562 and the Neuroblastoma cell line LAN6. Two independent replicates using different ATRX antibodies were performed in K562. Additionally, Native ChIP-seq of H3K9me3 in LAN6, ATRX WT and ATRX KO K562 cells was performed. Input samples were sequenced as control.

2016-04-05 | E-GEOD-70920 | biostudies-arrayexpress

Anatomic position determines oncogenic specificity in melanoma

Project description:Oncogenic alterations to DNA are not transforming in all cellular contexts. This may be due to pre-existing transcriptional programs in the cell of origin. Here, we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet, or under the nails. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma but CRKL amplifications in acral melanoma. We modeled these changes in transgenic zebrafish models and found that CRKL-driven tumors predominantly formed in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin/limb melanocytes, compared to body melanocytes, revealed a positional identity gene program typified by posterior HOX13 genes. This positional gene program synergized with CRKL to drive tumors at acral sites. Abrogation of this CRKL-driven program eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.

2022-01-12 | PXD027968 | Pride

Histone variant H2A.Z.2 mediates proliferation and drug sensitivity of malignant melanoma

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-07-01 | E-GEOD-59060 | biostudies-arrayexpress