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Psip1/p75 restrains Hox gene expression by recruiting both trithorax and polycomb group proteins

ABSTRACT: Psip1/p75 restrains Hox gene expression by recruiting both trithorax and polycomb group proteins

PROVIDER: PRJNA213236 | ENA |

REPOSITORIES: ENA

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Comparision of Psip1/p75 binding and Mll1 binding sites on Hox and non-Hox genes

Project description:Psip1/p75 binds to Hox genes and colocalizes with Mll1 and in Psip1 KO MEFs Mll1 occupancy is reduced over Hox genes Psip1/p75 ChIP using A300-848 abtibody (recognises p75 isoform of Psip1) and Mll1 ChIP from WT and Psip1 KO MEFs ChIP-chip

2014-06-27 | E-GEOD-49179 | biostudies-arrayexpress

Psip1/Ledgf p75 restrains Hox gene expression by recruiting both trithorax and polycomb group proteins.

Project description:Trithorax and polycomb group proteins are generally thought to antagonize one another. The trithorax family member MLL (myeloid/lymphoid or mixed-lineage leukemia) is presumed to activate Hox expression, counteracting polycomb-mediated repression. PC4 and SF2 interacting protein 1 (PSIP1)/p75, also known as LEDGF, whose PWWP domain binds to H3K36me3, interacts with MLL and tethers MLL fusion proteins to HOXA9 in leukaemias. Here we show, unexpectedly, that Psip1/p75 regulates homeotic genes by recruiting not only MLL complexes, but also the polycomb group protein Bmi1. In Psip1(-/-) cells binding of Mll1/2, Bmi1 and the co-repressor Ctbp1 at Hox loci are all abrogated and Hoxa and Hoxd mRNA expression increased. Our data not only reveal a potential mechanism of action for Psip1 in the regulation of Hox genes but also suggest an unexpected interplay between proteins usually considered as transcriptional activators and repressors.

| S-EPMC4132756 | biostudies-literature

PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes

Project description:Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in breast cancer initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in breast cancer progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma. Survival data analyses indicated that the levels of PSIP1 showed a negative association with TNBC patient survival. Depletion of PSIP1/p75 significantly reduced the tumorigenicity and metastatic properties of TNBC cell lines while its over-expression promoted tumorigenicity. Further, gene expression studies revealed that PSIP1 regulates the expression of genes controlling cell-cycle progression, cell migration, and invasion. Finally, by interacting with RNA polymerase II, PSIP1/p75 facilitates the association of RNA pol II to the promoter of cell cycle genes and thereby regulates their transcription. Our findings demonstrate an important role of PSIP1/p75 in TNBC tumorigenicity by promoting the expression of genes that control the cell cycle and tumor metastasis.

2017-06-06 | GSE99699 | GEO

Comparision of Psip1/p75 binding and Mll1 binding sites on Hox and non-Hox genes

Project description:Psip1/p75 binds to Hox genes and colocalizes with Mll1 and in Psip1 KO MEFs Mll1 occupancy is reduced over Hox genes

2014-06-27 | GSE49179 | GEO

Psip1/p75 restrains Hox gene expression by recruiting both trithorax and polycomb group proteins

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

2014-06-27 | E-GEOD-49182 | biostudies-arrayexpress

Psip1/p75 restrains Hox gene expression by recruiting both trithorax and polycomb group proteins

Project description:This SuperSeries is composed of the SubSeries listed below.

2014-06-27 | GSE49182 | GEO

LEDGF/p75 is Dispensable for Hematopoiesis but Essential for MLL-rearranged Leukemogenesis

Project description:Mixed-lineage leukemia (MLL) represents a genetically distinct and aggressive subset of human acute leukemia carrying chromosomal translocations of the MLL gene. These translocations result in oncogenic fusions that mediate aberrant recruitment of transcription machinery to MLL target genes. The N-terminus of MLL and MLL-fusions form a complex with Lens Epithelium-Derived Growth Factor (LEDGF/p75; encoded by the Psip1 gene) and MENIN. This complex contributes to the association of MLL and MLL-fusion multiprotein complexes with chromatin. Several studies have shown that both MENIN and LEDGF/p75 are required for efficient MLL fusion-mediated transformation and for the expression of downstream MLL-regulated genes like HOXA9 and MEIS1. In light of the development of a therapeutic strategy targeting this complex, understanding the function of LEDGF/p75 in normal hematopoiesis is crucial. We generated a conditional Psip1 knockout mouse model in the hematopoietic compartment and examined the effects of LEDGF/p75 depletion in postnatal hematopoiesis and the initiation of MLL leukemogenesis. Psip1 knockout mice were viable but showed several defects in hematopoiesis, reduced colony-forming activity in vitro, decreased expression of Hox genes in hematopoietic stem cells and decreased MLL occupancy at MLL target genes. Finally, in vitro and in vivo experiments showed that LEDGF/p75 is dispensable for steady state hematopoiesis but essential for the initiation of MLL-mediated leukemia. These data corroborate the MLL-LEDGF/p75 interaction as novel target for the treatment of MLL-rearranged leukemia.

2017-09-30 | GSE104138 | GEO

Comparision of Psip1/p75, Mll and Menin binding on the Hox and non-Hox genes

Project description:Menin binding pattern in WT and Psip1 KO MEFs Menin occupancy is studied over Hox genes Menin ChIP from WT and Psip1 KO MEFs ChIP-chip

2014-06-27 | E-GEOD-49180 | biostudies-arrayexpress

Comparision of Psip1/p75, Mll and Menin binding on the Hox and non-Hox genes

Project description:Menin binding pattern in WT and Psip1 KO MEFs Menin occupancy is studied over Hox genes

2014-06-27 | GSE49180 | GEO

Olfactory Enshealting Cells : p75 High vs p75 Low cells population

Project description:Comparative gene expression profiling of olfactory enshealting cells : p75 High vs p75 Low cells population

2011-07-20 | GSE30797 | GEO