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The PIAS-like coactivator Zmiz1 directly and selectively coregulates Notch1 in T-cell development and leukemia

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE66147 | GEO | 2015/10/28

SECONDARY ACCESSION(S): PRJNA275964

REPOSITORIES: GEO

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The PIAS-like coactivator Zmiz1 directly and selectively coregulates Notch1 in T-cell development and leukemia

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

2015-10-28 | E-GEOD-66147 | biostudies-arrayexpress

The PIAS-like coactivator Zmiz1 directly and selectively coregulates Notch1 in T-cell development and leukemia [ChIP-Seq]

Project description:The most recurrently mutated oncogene in T-cell acute lymphoblastic leukemia (T-ALL) is NOTCH1. The core Notch complex consists of an ICN protein, a Maml cofactor, and the DNA binding factor Rbpj. The known direct cofactors of Notch appear to act nonselectively, homogeneously driving Notch gene expression functions. It is unclear whether there are direct cofactors of Notch that act selectively and heterogeneously regulate ICN. We discovered that Zmiz1, a Protein Inhibitor of Activated STAT (PIAS)-like coactivator, directly bound ICN1. In order to determine whether this interaction occured at chromatin, we performed ChIP-Seq. We identified significant overlap between ICN1, Rbpj, and Zmiz1 peaks. 75% of overlapping ICN1/Rbpj peaks overlapped with Zmiz1 (HA) peaks (273 peaks). The size of Zmiz1 (HA) peaks had moderate correlation with the size of Rbpj and ICN1 peaks. Like Rbpj and ICN1 peaks, Zmiz1 (HA) peaks were associated with activating H3K27ac, H3K4me1, and H3K4me3 chromatin marks and were devoid of repressive H3K27me3 marks. These data suggest that Zmiz1 is a selective Notch regulator. It co-binds only a subset of ICN1 and Rbpj-regulated sites. Zmiz1, ICN1, Rbpj, histone mehylation ChIP-Seq in murine T-ALL cell line

2015-10-28 | E-GEOD-66146 | biostudies-arrayexpress

The PIAS-like coactivator Zmiz1 directly and selectively coregulates Notch1 in T-cell development and leukemia [RNA-Seq]

Project description:The most recurrently mutated oncogene in T-cell acute lymphoblastic leukemia (T-ALL) is NOTCH1. The core Notch complex consists of an ICN protein, a Maml cofactor, and the DNA binding factor Rbpj. The known direct cofactors of Notch appear to act nonselectively, homogeneously driving Notch gene expression functions. It is unclear whether there are direct cofactors of Notch that act selectively and heterogeneously regulate ICN. We discovered that Zmiz1, a Protein Inhibitor of Activated STAT (PIAS)-like coactivator, directly bound ICN1. ChIP-Seq showed that Zmiz1 selectively co-bound only a subset of Notch-regulated enhancers. This led to hypothesize that Zmiz1 regulates only a subset of Notch1 target genes. To investigate this, we performed RNA-Seq on four 8946 cell linesin which L1601P (activated Notch1) or Zmiz1 were expressed alone or in combination. Zmiz1 induced ~10% of Notch target genes. The Notch target gene that was most strongly induced by Zmiz1 was Myc. Our data suggest that Zmiz1 selectively amplifies a subset of Notch target genes with strong amplification of Myc. RNA-Seq in a murine T-ALL cell line

2015-10-28 | E-GEOD-66145 | biostudies-arrayexpress

The PIAS-like coactivator Zmiz1 directly and selectively coregulates Notch1 in T-cell development and leukemia [ChIP-Seq]

2015-10-28 | GSE66146 | GEO

The PIAS-like coactivator Zmiz1 directly and selectively coregulates Notch1 in T-cell development and leukemia [RNA-Seq]

Project description:The most recurrently mutated oncogene in T-cell acute lymphoblastic leukemia (T-ALL) is NOTCH1. The core Notch complex consists of an ICN protein, a Maml cofactor, and the DNA binding factor Rbpj. The known direct cofactors of Notch appear to act nonselectively, homogeneously driving Notch gene expression functions. It is unclear whether there are direct cofactors of Notch that act selectively and heterogeneously regulate ICN. We discovered that Zmiz1, a Protein Inhibitor of Activated STAT (PIAS)-like coactivator, directly bound ICN1. ChIP-Seq showed that Zmiz1 selectively co-bound only a subset of Notch-regulated enhancers. This led to hypothesize that Zmiz1 regulates only a subset of Notch1 target genes. To investigate this, we performed RNA-Seq on four 8946 cell linesin which L1601P (activated Notch1) or Zmiz1 were expressed alone or in combination. Zmiz1 induced ~10% of Notch target genes. The Notch target gene that was most strongly induced by Zmiz1 was Myc. Our data suggest that Zmiz1 selectively amplifies a subset of Notch target genes with strong amplification of Myc.

2015-10-28 | GSE66145 | GEO