Ontology highlight
ABSTRACT:
PROVIDER: PRJNA578485 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Allele-specific binding and expression in APOC3, APOA4, MYOD1, and HBB locus
| PRJNA752114 | ENA
Project description:Quantitative proteomics analysis for dcas9 captured locus specific binding proteins with K562 cell line. The locus includes "HBB, HBG, HBD and the enhancer regions" .
2017-07-17 | MSV000081339 | MassIVE
Project description:Mammalian chromosome replication starts from distinct sites, but the principles governing initiation site selection are unclear because proteins essential for DNA replication do not exhibit sequence-specific DNA binding. We identified a replication initiation determinant (RepID) protein that binds a subset of replication initiation sites. A large fraction of RepID binding sites share a common G-rich motif and exhibit elevated replication initiation. RepID is required for initiation of DNA replication from Rep-ID bound replication origins, including the origin at the human beta-globin (HBB) locus. At HBB, RepID is involved in an interaction between the replication origin (Rep-P) and the locus control region. RepID depleted murine embryonic fibroblasts exhibit abnormal replication fork progression and fewer replication initiation events. These observations are consistent with a model suggesting that RepID facilitates replication initiation at a distinct group of human replication origins.
2016-06-02 | GSE80298 | GEO
Project description:Mammalian chromosome replication starts from distinct sites, but the principles governing initiation site selection are unclear because proteins essential for DNA replication do not exhibit sequence-specific DNA binding. We identified a replication initiation determinant (RepID) protein that binds a subset of replication initiation sites. A large fraction of RepID binding sites share a common G-rich motif and exhibit elevated replication initiation. RepID is required for initiation of DNA replication from Rep-ID bound replication origins, including the origin at the human beta-globin (HBB) locus. At HBB, RepID is involved in an interaction between the replication origin (Rep-P) and the locus control region. RepID depleted murine embryonic fibroblasts exhibit abnormal replication fork progression and fewer replication initiation events. These observations are consistent with a model suggesting that RepID facilitates replication initiation at a distinct group of human replication origins. Nascent strands were purified with the lambda exonuclease methods from HCT116 cells and sequenced. Chromatin from unsyncrhonized untreated cultures of U2OS cells was subjected to ChIP-Seq with antibody directed against RepID/PHIP
2016-06-02 | E-GEOD-80298 | biostudies-arrayexpress
Project description:Genome-wide association studies (GWAS) are identifying genetic predisposition to various diseases. The rs1859962 single nucleotide polymorphism (SNP) part of the 17q24.3 locus is a risk factor for prostate cancer (PCa). It defines a 130kb linkage disequilibrium (LD) block that lies in a ~2Mb gene desert area. Despite a role for the proximal SOX9 gene in PCa development, the functional biology driving the risk of this 17q24.3 risk locus is unknown. In the present study, we integrate genome-wide chromatin landscape datasets, namely epigenomes and chromatin openness from diverse cell-types to identify one PCa specific enhancer within the rs1859962 risk LD block. We reveal that this enhancer is part of a 1Mb chromatin loop with the SOX9 gene in PCa cells. The rs8072254 and rs1859961 SNPs part of this LD block map to this enhancer and impose allele-specific gene expression. The variant allele of rs1859961 directly decreases FoxA1 binding while increasing AP-1 binding compared to the reference allele. This latter is key in driving allele-specific gene expression. Together, our results demonstrate the risk associated with the PCa rs1859962 risk LD block is accounted for by multiple genetic variants mapping to a unique enhancer looping to the SOX9 oncogene. Allele-specific recruitment of the transcription factor AP-1 accounts in part for the increased enhancer activity ascribed to this PCa risk LD block. This further demonstrates that an integrative genomics approach can identify the functional biology disrupted by genetic risk-variants. Examination of histone modification H3K36me3 in the prostate cancer LNCaP cell line under DHT treatment.
2012-06-03 | E-GEOD-35829 | biostudies-arrayexpress
Project description:Basic helix-loop-helix (bHLH) pioneer transcription factors Myod1 and Ascl1 are biochemically related but produce fundamentally different outcomes when expressed in fibroblasts: Myod1 produces muscle cells and Ascl1 induces neurons. Here, we sought to investigate the molecular mechanisms explaining the differential activity. Surprisingly, we found a large overlap in the overall binding patterns of Ascl1 and Myod1 in fibroblasts, with both transcription factors accessing both neuronal and myogenic targets. We also observed similar changes in chromatin accessibility and transcriptional activation. Yet, Myod1 predominantly induced a muscle program and Ascl1 a neuronal program. We found that differences in binding affinity at key targets resulted in largely distinct reprogramming outcomes. Accordingly, exchanging Myod1’s C-terminal protein-protein interacting domain and DNA-binding basic domain with those of Ascl1 induces an Ascl1-like binding and converts Myod1 into a pro-neuronal factor. Finally, we found that co-expression of Myod1 with the transcriptional repressor Myt1l inhibits induction of the muscle program and yields functional neuronal cells. Our findings are compatible with the notion that pioneer factor activity is associated with high-affinity protein-DNA and suggest that promiscuous binding of pioneer factors can induce unspecific lineage features which need to be kept in check by co-factor interactions.
2020-02-03 | GSE126410 | GEO
Project description:Basic helix-loop-helix (bHLH) pioneer transcription factors Myod1 and Ascl1 are biochemically related but produce fundamentally different outcomes when expressed in fibroblasts: Myod1 produces muscle cells and Ascl1 induces neurons. Here, we sought to investigate the molecular mechanisms explaining the differential activity. Surprisingly, we found a large overlap in the overall binding patterns of Ascl1 and Myod1 in fibroblasts, with both transcription factors accessing both neuronal and myogenic targets. We also observed similar changes in chromatin accessibility and transcriptional activation. Yet, Myod1 predominantly induced a muscle program and Ascl1 a neuronal program. We found that differences in binding affinity at key targets resulted in largely distinct reprogramming outcomes. Accordingly, exchanging Myod1’s C-terminal protein-protein interacting domain and DNA-binding basic domain with those of Ascl1 induces an Ascl1-like binding and converts Myod1 into a pro-neuronal factor. Finally, we found that co-expression of Myod1 with the transcriptional repressor Myt1l inhibits induction of the muscle program and yields functional neuronal cells. Our findings are compatible with the notion that pioneer factor activity is associated with high-affinity protein-DNA and suggest that promiscuous binding of pioneer factors can induce unspecific lineage features which need to be kept in check by co-factor interactions.
2020-02-03 | GSE126411 | GEO
Project description:Basic helix-loop-helix (bHLH) pioneer transcription factors Myod1 and Ascl1 are biochemically related but produce fundamentally different outcomes when expressed in fibroblasts: Myod1 produces muscle cells and Ascl1 induces neurons. Here, we sought to investigate the molecular mechanisms explaining the differential activity. Surprisingly, we found a large overlap in the overall binding patterns of Ascl1 and Myod1 in fibroblasts, with both transcription factors accessing both neuronal and myogenic targets. We also observed similar changes in chromatin accessibility and transcriptional activation. Yet, Myod1 predominantly induced a muscle program and Ascl1 a neuronal program. We found that differences in binding affinity at key targets resulted in largely distinct reprogramming outcomes. Accordingly, exchanging Myod1’s C-terminal protein-protein interacting domain and DNA-binding basic domain with those of Ascl1 induces an Ascl1-like binding and converts Myod1 into a pro-neuronal factor. Finally, we found that co-expression of Myod1 with the transcriptional repressor Myt1l inhibits induction of the muscle program and yields functional neuronal cells. Our findings are compatible with the notion that pioneer factor activity is associated with high-affinity protein-DNA and suggest that promiscuous binding of pioneer factors can induce unspecific lineage features which need to be kept in check by co-factor interactions.
2020-02-03 | GSE126413 | GEO
Project description:Basic helix-loop-helix (bHLH) pioneer transcription factors Myod1 and Ascl1 are biochemically related but produce fundamentally different outcomes when expressed in fibroblasts: Myod1 produces muscle cells and Ascl1 induces neurons. Here, we sought to investigate the molecular mechanisms explaining the differential activity. Surprisingly, we found a large overlap in the overall binding patterns of Ascl1 and Myod1 in fibroblasts, with both transcription factors accessing both neuronal and myogenic targets. We also observed similar changes in chromatin accessibility and transcriptional activation. Yet, Myod1 predominantly induced a muscle program and Ascl1 a neuronal program. We found that differences in binding affinity at key targets resulted in largely distinct reprogramming outcomes. Accordingly, exchanging Myod1’s C-terminal protein-protein interacting domain and DNA-binding basic domain with those of Ascl1 induces an Ascl1-like binding and converts Myod1 into a pro-neuronal factor. Finally, we found that co-expression of Myod1 with the transcriptional repressor Myt1l inhibits induction of the muscle program and yields functional neuronal cells. Our findings are compatible with the notion that pioneer factor activity is associated with high-affinity protein-DNA and suggest that promiscuous binding of pioneer factors can induce unspecific lineage features which need to be kept in check by co-factor interactions.
2020-02-03 | GSE140381 | GEO