Genome-wide mapping of FOXM1 binding reveals co-binding with estrogen receptor alpha in breast cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Dario Beraldi
PROVIDER: E-GEOD-40767 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The forkhead transcription factor FOXM1 is a key regulator of the cell cycle and is overexpressed in cancer. Increased levels of FOXM1 are associated with both poor prognosis and oestrogen receptor (ERalpha) status in primary breast cancer. In this study, we map FOXM1 binding genome wide in both ERalpha-positive (MCF-7) and -negative (MDA-MB-231) breast cancer cells. We identify a common set of FOXM1 binding events at cell cycle-regulating genes, but in addition, in MCF-7 cells we find a high level of concordance with ERalpha-binding regions. FOXM1 binding at these co-binding sites is dependent on ERalpha binding, as depletion of ER protein levels reduced FOXM1 binding. FOXM1 interacts directly with both ERalpha co-activator CARM1 and is required for H3 arginine methylation at the ERalpha complex. Inhibition of FOXM1 activity with the ligand thiostrepton resulted in decreased FOXM1 binding at cca. 1400 sites genome wide and reduced expression of genes correlated with poor prognosis in ERalpha-positive tumour samples. These data demonstrate a novel role for the forkhead protein FOXM1 as an ERalpha cofactor and provide insight into the role of FOXM1 in ERalpha-positive breast cancer. The FOXM1-binding sites were mapped by ChIP-Seq in MCF-7 and MDA-MB-231 cells. Cells were treated either with thiostrepton, a FOXM1 inhibitor, or with DMSO (as control). Four replicates were performed in MCF7 cells and two replicates in MDA-MB-231 cells.
2013-01-07 | E-GEOD-40762 | biostudies-arrayexpress
Project description:The forkhead transcription factor FOXM1 is a key regulator of the cell cycle and is overexpressed in cancer. Increased levels of FOXM1 are associated with both poor prognosis and oestrogen receptor (ERalpha) status in primary breast cancer. In this study, we map FOXM1 binding genome wide in both ERalpha-positive (MCF-7) and -negative (MDA-MB-231) breast cancer cells. We identify a common set of FOXM1 binding events at cell cycle-regulating genes, but in addition, in MCF-7 cells we find a high level of concordance with ERalpha-binding regions. FOXM1 binding at these co-binding sites is dependent on ERalpha binding, as depletion of ER protein levels reduced FOXM1 binding. FOXM1 interacts directly with both ERalpha co-activator CARM1 and is required for H3 arginine methylation at the ERalpha complex. Inhibition of FOXM1 activity with the ligand thiostrepton resulted in decreased FOXM1 binding at cca. 1400 sites genome wide and reduced expression of genes correlated with poor prognosis in ERalpha-positive tumour samples. These data demonstrate a novel role for the forkhead protein FOXM1 as an ERalpha cofactor and provide insight into the role of FOXM1 in ERalpha-positive breast cancer. MCF-7 cells were treated with either thiostrepton or DMSO for 6 hr. Each treatment was carried out in replicates of 6.
2013-01-07 | E-GEOD-40766 | biostudies-arrayexpress
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2014-10-02 | E-GEOD-43283 | biostudies-arrayexpress
Project description:Dark-grown seedlings exhibit skotomorphogenic development. Genetic and molecular evidence indicates that a quartet of Arabidopsis Phytochrome (phy)-Interacting bHLH Factors (PIF4, 3, 4 and 5) are critically necessary to maintaining this developmental state, and that light activation of phy induces a switch to photomorphogenic development by inducing rapid degradation of the PIFs. Here, using combined ChIP-seq and RNA-seq analyses, we have identified genes that are direct targets of PIF4 transcriptional regulation, and we provide evidence that the quartet collectively regulate these genes by shared, direct binding to the target promoters in promoting skotomorphogenesis. Three biological replicates data of PIF4-binding sites were collected by comparing the parallel ChIP samples from Myc-epitope-tagged-PIF4 (P1M) overexpressing transgenic seedlings and the wild-type (WT) control.
2014-10-02 | E-GEOD-43284 | biostudies-arrayexpress
Project description:DELLA proteins act as hubs that relay environmental information to the multiple transcriptional circuits that control growth and development through physical interaction with transcription factors from different families. We have analyzed the presence of one DELLA protein at the Arabidopsis genome by chromatin immunoprecipitation coupled to large-scale sequencing and we find that it binds at the promoters of multiple genes. Enrichment analysis shows a strong preference for cis elements recognized by specific transcription factor families. In particular, we demonstrate that DELLA proteins are recruited by type-B ARABIDOPSIS RESPONSE REGULATORS (ARR) to the promoters of cytokinin-regulated genes, where they act as transcriptional co-activators. The biological relevance of this mechanism is underpinned by the necessity of simultaneous presence of DELLAs and ARRs to restrict root meristem growth and to promote photomorphogenesis. Provided are 3 biological replicates analysing RGA binding sites in Arabidopsis seedlings. ChIP-seq was performed on plants expressing RGA-GFP under the native RGA promoter and on non-transgenic control plants as reference
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Project description:Sequence data represent a profile of AR network targets in proliferating and non-proliferating P17 cells without cross linking AR to DNA prior to purification. P17 cells were derived from the mouse epididymal cell line PC1 by genetic modification to express a tagged wild type mouse AR cDNA (N-TAP-mAR). N-TAP-mAR allows purification of multi-protein complexes and their genomic targets with FLAG antibody coupled magnetic beads under native conditions. comparison of AR targets in proliferating versus non-proliferating cells using the PC1 WT cell line (not expressing a tagged AR) as a negative control.
2015-06-11 | E-GEOD-38656 | biostudies-arrayexpress
Project description:Dark-grown seedlings exhibit skotomorphogenic development. Genetic and molecular evidence indicates that a quartet of Arabidopsis Phytochrome (phy)-Interacting bHLH Factors (PIF1, 3, 4 and 5) are critically necessary to maintaining this developmental state, and that light activation of phy induces a switch to photomorphogenic development by inducing rapid degradation of the PIFs. Here, using combined ChIP-seq and RNA-seq analyses, we have identified genes that are direct targets of PIF3 transcriptional regulation, and we provide evidence that the quartet collectively regulate these genes by shared, direct binding to the target promoters in promoting skotomorphogenesis. Four biological replicates data of PIF3-binding sites were collected by comparing the parallel ChIP samples from transgenic seedlings overexpressing Myc-epitope-tagged PIF3 (35S:PIF3-5xMyc, P3M) in pif3-3 null mutant background and the wild-type (WT) control.
2013-02-01 | E-GEOD-39215 | biostudies-arrayexpress
Project description:Estrogen Receptor (ESR1) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcription events that promote tumor growth. Differences in enhancer occupancy by ESR1, contribute to the diverse expression profiles and clinical outcome observed in breast cancer patients. GATA3 is an ESR1 co-operating transcription factor mutated in breast tumors, however its genomic properties are not fully defined. In order to investigate the composition of enhancers involved in estrogen-induced transcription and the potential role of GATA3, we performed extensive ChIP-sequencing in unstimulated breast cancer cells and following estrogen treatment. We find that GATA3 is pivotal in mediating enhancer accessibility at regulatory regions involved in ESR1-mediated transcription. GATA3 silencing resulted in a global redistribution of co-factors and active histone marks prior to estrogen stimulation. These global genomic changes altered the ESR1 binding profile that subsequently occurred following estrogen, with events exhibiting both loss and gain in binding affinity, implying a GATA3 mediated re-distribution of ESR1 binding. The GATA3-mediated re-distributed ESR1 profile correlated with changes in gene expression, suggestive of its functionality. Chromatin loops at the TFF locus involving ESR1 bound enhancers occurred independently of ESR1 when GATA3 was silenced, indicating that GATA3, when present on the chromatin, may serve as a licensing factor for estrogen- ESR1 mediated interactions between cis-regulatory elements. Together these experiments suggest that GATA3 directly impacts ESR1 enhancer accessibility and may potentially explain the contribution of mutant-GATA3 in the heterogeneity of ESR1+ breast cancer. MCF7 cells were transfected with siRNA and cultured in hormone deprived conditions for a further 3 days. Cells were subsequently treated with 100nM estrogen (E2) or control (Veh) for 6 hrs. We performed two independent biological experiments each using three different siRNAs against GATA3 individually (six siGATA3 replicates in total). For siControl we used RNA from five biological replicates.
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
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