Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA400173 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To determine if there is a physical interaction between the FOXF1 promoter and putative enhancer sequences ~250kb upstream of the promoter chromosome conformation capture-on-chip (4C) analysis was performed. An unanticipated and tremendous amount of the non-coding sequences of the human genome are transcribed. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides and their functions remain enigmatic. We demonstrate that deletions of lncRNA genes cause a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV), with parent of origin effects. We identify non-coding overlapping deletions 250 kb upstream to FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete a fetal lung-specific EST, part of an lncRNA. These deletions define distant cis-regulatory region that harbors a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter, consistent with the absence of the fetal lung-transcribed lncRNA perturbing FOXF1 regulation. LncRNA-mediated chromatin interactions may be responsible for position effect phenomenon and potentially cause many disorders of human development. 4C analysis using 16q24.1 specific 3x720K arrays demonstrated physical interaction between the FOXF1 promoter and distant putative regulatory sequences, about 250 kb upstream in human pulomonary microvascular endothelial cells; 2 biological replicates performed; this chromatin looping was not detected in lymphoblasts that do not express FOXF1 and hence serve as a negative control.
2012-07-10 | E-GEOD-39256 | biostudies-arrayexpress
Project description:Stochastic activation of clustered Protocadherin (Pcdh) α, β, and γ genes generates a cell-surface identity code in individual neurons that functions in neural circuit assembly. Here, we show that Pcdhα gene choice involves the activation of an antisense promoter located in the first exon of each Pcdhα alternate gene. Transcription of an antisense long noncoding RNA (lncRNA) from this antisense promoter extends through the sense promoter, leading to DNA demethylation of the CTCF binding sites proximal to each promoter. Demethylation-dependent CTCF binding to both promoters facilitates cohesin-mediated DNA looping with a distal enhancer (HS5-1), locking in the transcriptional state of the chosen Pcdhα gene. Uncoupling DNA demethylation from antisense transcription by Tet3 overexpression in mouse olfactory neurons promotes CTCF binding to all Pcdhα promoters, resulting in proximity-biased DNA looping of the HS5-1 enhancer. Thus, antisense transcription-mediated promoter demethylation functions as a mechanism for distance-independent enhancer/promoter DNA looping to ensure stochastic Pcdhα promoter choice.
2019-04-15 | GSE115862 | GEO
Project description:Cancer cells frequently depend on chromatin regulatory activities to maintain a malignant phenotype. Here, we show that leukemia cells require the mammalian SWI/SNF chromatin remodeling complex for their survival and aberrant self-renewal potential. While Brg1, an ATPase subunit of SWI/SNF, is known to suppress tumor formation in several cancer types, we found that leukemia cells instead rely on Brg1 to support their oncogenic transcriptional program, which includes Myc as one of its key targets. To account for this context-specific function, we identify a cluster of lineage-specific enhancers located 1.7 megabases downstream of Myc that are occupied by SWI/SNF, as well as the BET protein Brd4. Brg1 is required at these distal elements to maintain transcription factor occupancy and for long-range chromatin looping interactions with the Myc promoter. Notably, these distal Myc enhancers coincide with a region that is focally amplified in 3% of acute myeloid leukemia. Together, these findings define a leukemia maintenance function for SWI/SNF that is linked to enhancer-mediated gene regulation, providing general insights into how cancer cells exploit transcriptional coactivators to maintain oncogenic gene expression programs Enhancer usually regulates its targets through physical contact/interaction. In order to study chromosome conformation of Myc locus and potential distal enhancer E1-E5 region in murine AML cells, we utilize the high resolution 4C-seq and analysis pipeline to search cis elements that physical interact with Myc and E1-E5 region through setting up two individual viewpoints in these two regions.
2013-12-02 | E-GEOD-52595 | biostudies-arrayexpress
Project description:Enhancers play key roles in gene regulation. However, comprehensive enhancer discovery is challenging because most enhancers, especially those affected in complex diseases, have weak effects on gene expression. Through gene regulatory network modeling, we identified that dynamic cell state transitions, a critical missing component in prevalent enhancer discovery strategies, can be utilized to improve the cells’ sensitivity to enhancer perturbation. Guided by the modeling results, we performed a mid-transition CRISPRi-based enhancer screen utilizing human embryonic stem cell definitive endoderm differentiation as a dynamic transition system. The screen discovered a comprehensive set of enhancers (4 to 9 per locus) for each of the core lineage-specifying transcription factors (TFs), including many enhancers with weak to moderate effects. Integrating the screening results with enhancer activity measurements (ATAC-seq, H3K27ac ChIP-seq) and three-dimensional enhancer-promoter interaction information (CTCF looping, Hi-C), we were able to develop a CTCF loop-constrained Interaction Activity (CIA) model that can better predict functional enhancers compared to models that rely on Hi-C-based enhancer-promoter contact frequency. Together, our dynamic network-guided enhancer screen and the CIA enhancer prediction model provide generalizable strategies for sensitive and more comprehensive enhancer discovery in both normal and pathological cell state transitions.
2023-06-17 | PXD043070 | Pride
Project description:FOXF1 promoter-putative enhancer chromatin looping
| PRJNA170423 | ENA
Project description:The most prominent model for long-range enhancer regulation involves direct enhancer-promoter interaction by looping out the intervening chromatin. Using a synthetic biology approach, we have determined that a chromatin unfolding bteween Shh and its enhancers is regulated specifically by the Shh-Brain-Enhancers and is mediated by the recruitment of Poly (ADP-Ribose) Polymerase 1. This ‘chromatin unfolding’ model represents a new mechanism of long-range enhancer-promoter communication in addition to the looping and tracking models. Using 5C study the enhancer-driven activation of the Sonic hedgehog gene (Shh)
2016-11-02 | GSE89388 | GEO
Project description:Chromosomal rearrangements are a frequent cause of oncogene deregulation in human malignancies. Overexpression of EVI1 is found in a subgroup of acute myeloid leukemia (AML) with 3q26 chromosomal rearrangements which are often therapy resistant. In a cohort of primary t(3;8)(q26;q24) AML samples we observed the translocation of a MYC super-enhancer to EVI1. We generated a patient-based t(3;8)(q26;q24) model in vitro using CRISPR-Cas9 technology and demonstrated hyper-activation of EVI1 by the hijacked MYC super-enhancer. One MYC super-enhancer element in particular, which recruits early hematopoietic regulators, is critical for EVI1 expression and enhancer-promoter interaction. This interaction is facilitated by a CTCF-bound motif upstream of the EVI1 promoter that acts as an enhancer-docking site in t(3;8) AML. Genomic analyses of 3q26-rearranged AML samples point to a common mechanism by which EVI1 uses this CTCF-bound enhancer-docking site to hijack early hematopoietic enhancers.
| EGAS00001004808 | EGA
Project description:lncRNAs play important roles in various physiological and pathological processes. However, the detailed molecular mechanisms by which lncRNAs act are still incomplete. Here, we functionally characterized the nuclear-enriched lncRNA SNHG1 which is highly expressed in several types of cancer relative to surrounding normal tissues. SNHG1 was regulated by oncogenic factor c-Myc and could promote tumor growth. We found that SNHG1 was involved in the Akt signaling pathway through promoting the neighboring transcription of protein-coding gene SLC3A2 in cis, by binding to the Mediator complex to facilitate enhancer-promoter interaction. Transcriptome analysis further revealed that several stress response genes, as well as signaling pathways, were regulated by SNHG1. Importantly, SNHG1 coordinated the expression of ATF3 through preventing FUBP1 from binding to its upstream regulatory region. Collectively, our findings demonstrate that lncRNA SNHG1 can function both in cis and in trans with distinct mechanisms to promote tumorigenesis and progression. Even, Odd probes targeting SNHG1 sequence, and control probes targeting LacZ. Probes was coupled with biotin, the captured DNA was prepared for library then sequencing.
2016-08-20 | E-GEOD-85842 | biostudies-arrayexpress
Project description:Super-enhancers may regulate target genes through chromatin looping. We connected super-enhancers in the K562 chronic myelogenous leukemia cell line with chromatin interactions identified from Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) data. Gene expression at proximal elements that are connected with distal super-enhancers showed significantly higher cell-type specificity than at proximal elements connected with other elements or not involved in interaction. 4C and Episwitch analysis of chromatin interactions showed that certain chromatin interactions are cell-specific, but others are more general. While super-enhancers upstream of c-MYC at the MYC-335 element can be found in other cancers, only super-enhancers downstream of c-MYC can be found in K562. 4C analysis of the c-MYC promoter revealed no chromatin interactions that are directed upstream of c-MYC, but only downstream of c-MYC, in the PVT1 long non-coding RNA gene. Cell-specific usage of super-enhancers could explain why the MYC-335 element that is associated with many solid cancers such as colorectal cancer and breast cancer, but not with leukemia. Surprisingly, we found that a chromatin interaction between c-MYC and a c-MYC super-enhancer is lost in chronic myelogenous leukemia patient blood as compared with blood from individuals without the disease through Oxford Biodynamicsâ?? Episwitch analysis. These results provide evidence for fine-tuning of expression patterns, such as cell-specific regulation of target genes by distal super-enhancers through chromatin interactions and an association between chromatin interactions and disease, and highlight that super-enhancers are more complex than previously described. Examination of several chromatin interactions involving super-enhancers using 4C-Seq and Episwitch (TM)
2017-05-01 | E-GEOD-77125 | biostudies-arrayexpress
Project description:Epstein-Barr-Virus (EBV) Nuclear Antigens EBNALP and EBNA2 are co-expressed in EBV infected B-lymphocytes and are critical for Lymphoblastoid Cell Line (LCL) growth. EBNALP removes NCOR1 and RBPJ repressive complexes from promoter and enhancer sites and EBNA2 mostly activates transcription from distal enhancers. ChIP-seqs found EBNALP at 19,224 LCL sites, which were 33% promoter associated. EBNALP was associated with 10 transcription factor (TF) clusters that included YY1(63%), SP1(62%), PAX5(59%), BATF(50%), IRF4(49%), RBPJ(43%), ETS1(39%), PU.1(37%), RAD21(33%), NF-kB(31%), TBLR1(26%), ZNF143(24%), CTCF(23%), SMC3(21%), and EBF(17%). EBNALP sites had higher H3K4me3, H3K9ac, H3K27ac, H2Az, and RNA Pol II signals than EBNA2 sites and had similar transcription effects. EBNALP co-localized with 29% of 19,845 EBNA2 sites. EBNALP/EBNA2 sites were similar to EBNALP sites in promoter localization, associated cell TFs, Pol II, H3K4me3, H3K9ac, H3K27ac, and H2Az signals. EBNALP and EBNA2 promoter sites were more transcriptionally active than EBNALP or EBNA2 promoter sites. EBNALP was at the enhancer or promoter of myc and MYC affected genes, including cyclin D2, and bcl2. EBNALP at promoters with DNA looping and transcription factors, is positioned to deplete repressors from enhancers and promoters, enable chromatin remodeling, and transcription activation. Two EBNALP ChIP-seq replicates from IB4 LCL are analyzed in this study.
2013-07-31 | E-GEOD-49338 | biostudies-arrayexpress