HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA844555 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19520434_1.fastq.gz | Fastqsanger.gz | |||
| SRR19520434_2.fastq.gz | Fastqsanger.gz | |||
| SRR19520435_1.fastq.gz | Fastqsanger.gz | |||
| SRR19520435_2.fastq.gz | Fastqsanger.gz | |||
| SRR19520436_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 72 |
Similar Datasets
Project description:Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA, HOTAIR (HOX transcript antisense RNA), is exclusively expressed in gluteofemoral AT, where it is essential for adipocyte development. We find that HOTAIR interacts with Polycomb Repressive Complex 2 (PRC2) and identify core HOTAIR-PRC2 target genes involved in adipocyte lineage determination. Repression of target genes coincides with PRC2 promoter occupancy and H3K27 tri-methylation. HOTAIR is also involved in modifying the gluteal adipocyte transcriptome through alternative splicing. Gluteal-specific expression of HOTAIR is maintained by defined regions of open chromatin across the HOTAIR promoter. HOTAIR expression levels can be modified by hormonal (oestrogen, glucocorticoids) and genetic variation (rs1443512 is a HOTAIR eQTL associated with reduced gynoid fat mass in 25,200 individuals). These data identify HOTAIR as a dynamic regulator of the gluteal adipocyte transcriptome and epigenome with functional importance for human regional AT development.
2022-07-26 | GSE205350 | GEO
Project description:Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA HOTAIR (HOX transcript antisense RNA) is exclusively expressed in gluteofemoral AT, where it is essential for adipocyte development. We find that HOTAIR interacts with polycomb repressive complex 2 (PRC2) and we identify core HOTAIR-PRC2 target genes involved in adipocyte lineage determination. Repression of target genes coincides with PRC2 promoter occupancy and H3K27 trimethylation. HOTAIR is also involved in modifying the gluteal adipocyte transcriptome through alternative splicing. Gluteal-specific expression of HOTAIR is maintained by defined regions of open chromatin across the HOTAIR promoter. HOTAIR expression levels can be modified by hormonal (estrogen, glucocorticoids) and genetic variation (rs1443512 is a HOTAIR eQTL associated with reduced gynoid fat mass). These data identify HOTAIR as a dynamic regulator of the gluteal adipocyte transcriptome and epigenome with functional importance for human regional AT development.
| S-EPMC10073411 | biostudies-literature
Project description:Epithelial-to-mesenchymal transitions (EMT) underlie a loss of epithelial traits by normal cells during development and neoplastic cells during cancer metastasis. The long noncoding RNA HOTAIR triggers EMT, in part by serving as a scaffold for Polycomb Repressive Complex 2 (PRC2) and thus promoting repressive histone H3 Lys27 methylation. In addition to PRC2, HOTAIR interacts with the Lsd1 lysine demethylase, an epigenetic regulator of cell fate during development and differentiation. Here, we showed that HOTAIR requires the Lsd1-interacting domain, but not the PRC2-interacting domain, to promote migration of epithelial cells. Our results suggest that the HOTAIR-Lsd1 asociation redistributes Lsd1 on chromatin and hence reprograms the epithelial transcriptome.
2021-04-22 | GSE162937 | GEO
Project description:Accumulating evidence highlights the role of long non-coding RNAs (lncRNA) in cellular homeostasis, and their dysregulation in disease settings. Most lncRNAs function by interacting with proteins or protein complexes. While several orthogonal methods have been developed to identify these proteins, each method has its inherent strengths and limitations. Here, we combine two RNA-centric methods ChIRP-MS and RNA-BioID to obtain a comprehensive list of proteins that interact with the well-known lncRNA HOTAIR. Overexpression of HOTAIR has been associated with a metastasis-promoting phenotype in various cancers. Although HOTAIR is known to bind with PRC2 and LSD1 protein complexes, an unbiased and comprehensive method to map its interactome has not yet been performed. Both ChIRP-MS and RNA-BioID data sets show an association of HOTAIR with mitoribosomes, suggesting HOTAIR has functions independent of its (post-)transcriptional mode-of-action.
2022-02-15 | PXD029057 | Pride
Project description:The human long noncoding RNA (lncRNA) HOTAIR acts in trans to recruit the Polycomb Repressive Complex 2 (PRC2) to the HOXD gene cluster and promote gene silencing during development. In breast cancers, overexpression of HOTAIR increases metastatic potential via the repression of many additional genes. It has remained unclear what factors determine HOTAIR-dependent PRC2 activity at specific genomic loci, particularly when high levels of HOTAIR result in aberrant gene silencing. To identify additional proteins that contribute to the specific action of HOTAIR, we performed a quantitative proteomic analysis of the HOTAIR interactome. We found that the most specific interaction was between HOTAIR and the heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, a member of a family of proteins involved in nascent mRNA processing and RNA matchmaking. Our data suggest that A2/B1 are key contributors to HOTAIR-mediated chromatin regulation in breast cancer cells: A2/B1 knockdown reduces HOTAIR-dependent breast cancer cell invasion and decreases PRC2 activity at the majority of HOTAIR-dependent loci. We found that the B1 isoform, which differs from A2 by 12 additional amino acids, binds with highest specificity to HOTAIR. B1 also binds chromatin and associates preferentially with RNA transcripts of HOTAIR gene targets. We furthermore demonstrate a direct RNA-RNA interaction between HOTAIR and a target transcript that is enhanced by B1 binding. Together, these results suggest a model in which B1 matches HOTAIR with transcripts of target genes on chromatin, leading to repression by PRC2.
2016-05-09 | GSE73702 | GEO
Project description:HOTAIR is a scafold long non-coding RNA tethering PRC2 and Lsd1/REST/coREST complexes to gene promoters to repress transcription of genes involved in epithelial to mesenchymal transition (EMT). To decipher a role of the Lsd1 in HOTAIR function we generated epithelial cell lines expressing full length and truncated versions of HOTAIR missing first 5'-300 (Epi-HOTΔP) and last 3'-500 bp (Epi-HOTΔL) interacting with HOTAIR partners. These cell lines were further used to determine Lsd1 binding sites using chromatin immunoprecipitation approach.
2021-04-22 | GSE106262 | GEO
Project description:Accumulating evidence highlights the role of long non-coding RNAs (lncRNA) in cellular homeostasis, and their dysregulation in disease settings. Most lncRNAs function by interacting with proteins or protein complexes. While several orthogonal methods have been developed to identify these proteins, each method has its inherent strengths and limitations. Here, we combine two RNA-centric methods ChIRP-MS and RNA-BioID to obtain a comprehensive list of proteins that interact with the well-known lncRNA HOTAIR. Overexpression of HOTAIR has been associated with a metastasis-promoting phenotype in various cancers. Although HOTAIR is known to bind with PRC2 and LSD1 protein complexes, an unbiased and comprehensive method to map its interactome has not yet been performed. Both ChIRP-MS and RNA-BioID data sets show an association of HOTAIR with mitoribosomes, suggesting HOTAIR has functions independent of its (post-)transcriptional mode-of-action.
2022-02-15 | PXD029058 | Pride
Project description:Large intervening noncoding RNAs (lincRNAs) are pervasively transcribed in the genome yet their potential involvement in human disease is not well understood4,5. Recent studies of dosage compensation, imprinting, and homeotic gene expression suggest that individual lincRNAs can function as the interface between DNA and specific chromatin remodeling activities. Here we show that lincRNAs in the HOX loci become systematically dysregulated during breast cancer progression. The lincRNA termed HOTAIR is increased in expression in primary breast tumors and metastases, and HOTAIR expression level in primary tumors is a powerful predictor of eventual metastasis and death. Enforced expression of HOTAIR in epithelial cancer cells induced genome-wide re-targeting of Polycomb Repressive Complex 2 (PRC2) to an occupancy pattern more resembling embryonic fibroblasts, leading to altered histone H3 lysine 27 methylation, gene expression, and increased cancer invasiveness and metastasis in a manner dependent on PRC2. Conversely, loss of HOTAIR can inhibit cancer invasiveness, particularly in cells that possess excessive PRC2 activity. These findings suggest that lincRNAs play active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy. Comparision of MDA-MB-231 Breast Cancer Cells expressing vector or HOTAIR. Each cell line was subjected to ChIP-chip with anti-H3K27, SUZ12, and EZH2 and interrogated on whole genome promoter arrays
2010-03-16 | E-GEOD-20737 | biostudies-arrayexpress
Project description:Objective: Abdominal adiposity is strongly associated with diabetic and cardiovascular comorbidities. The long non-coding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is an important epigenetic regulator, with fat depot-specific expression between abdominal subcutaneous adipose tissue (SAT) and gluteal SAT. HOTAIR locates closely with HOXC13, known to strongly associated with human fat distribution. Here, we examined the phenotypic effects of HOTAIR overexpression on abdominal adipogenesis, and hypothesized that HOTAIR-mediated DNA methylation is correlated with transcriptome changes, leading to the regulation of specific genes and the functional pathways. Methods: The expression level of HOTAIR was compared among different fat-depots collected from six healthy, five severe obese, and five uremic subjects, and was correlated with dual-energy x-ray absorptiometry (DXA) defined regional adiposity. The human immortalized preadipocyte was used to assess the phenotypic effects of HOTAIR overexpression on abdominal adipogenesis. The integrative analysis of reduced representation bisulfite sequencing (RRBS) and RNA-sequencing was performed to identify putative genes that are epigenetically regulated by HOTAIR, and the associated signaling pathways. HOTAIR-repressed genes were further validated using RNA/chromatin immunoprecipitation with real-time qPCR and correlated with human body fat distribution. Results: We found that the expression of HOTAIR was high in gluteal SAT, and low in arm/abdominal SAT and visceral (omental) adipose tissue. It could be aberrantly increased in uremic arm SAT. Notably, in severe obese subjects we found that HOTAIR is lowly expressed in abdominal SAT correlating with a higher abdominal adiposity, whereas in uremic patients HOTAIR is highly expressed in arm SAT correlating with lower arm adiposity. HOTAIR overexpression in human immortalized abdominal preadipocyte remarkably suppresses the in vitro adipogenesis. Overall the differentially methylated genes were functionally enriched for nervous system development. We specifically identified 10 HOTAIR-mediated genes showing strong changes of DNA methylation associated with gene expression during abdominal adipogenesis, suggesting potential epigenetic regulation. Two HOTAIR-repressed genes, SLITRK4 and PITPNC1, were further highlighted and validated; presenting an obesity-driven fat-depot specific expression pattern positively correlated with the central body fat distribution. Conclusions: Our study indicated that HOTAIR is an important regulator for abdominal adipogenesis via intricate DNA methylation likely to associate with transcriptional regulation of specific genes, such as SLITRK4 and PITPNC1.
2022-04-20 | GSE186159 | GEO
Project description:Large intervening noncoding RNAs (lincRNAs) are pervasively transcribed in the genome yet their potential involvement in human disease is not well understood4,5. Recent studies of dosage compensation, imprinting, and homeotic gene expression suggest that individual lincRNAs can function as the interface between DNA and specific chromatin remodeling activities. Here we show that lincRNAs in the HOX loci become systematically dysregulated during breast cancer progression. The lincRNA termed HOTAIR is increased in expression in primary breast tumors and metastases, and HOTAIR expression level in primary tumors is a powerful predictor of eventual metastasis and death. Enforced expression of HOTAIR in epithelial cancer cells induced genome-wide re-targeting of Polycomb Repressive Complex 2 (PRC2) to an occupancy pattern more resembling embryonic fibroblasts, leading to altered histone H3 lysine 27 methylation, gene expression, and increased cancer invasiveness and metastasis in a manner dependent on PRC2. Conversely, loss of HOTAIR can inhibit cancer invasiveness, particularly in cells that possess excessive PRC2 activity. These findings suggest that lincRNAs play active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.
2010-03-16 | GSE20737 | GEO