Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA255296 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:MMSET I acts as an oncoprotein and regulates GLO1 expression in t(4 14) multiple myeloma cells
| PRJNA385086 | ENA
Project description:The MMSET (Multiple Myeloma SET domain) protein is overexpressed in multiple myeloma patients with the translocation t(4;14). Although studies have shown the involvement of MMSET/WHSC1 in development, its mode of action in the pathogenesis of multiple myeloma (MM) is largely unknown. We found that MMSET is a major regulator of chromatin structure and transcription in t(4;14) MM cells. High levels of MMSET correlate with an increase in lysine 36 methylation of histone H3 and a decrease in lysine 27 methylation across the genome, leading to a more open structural state of the chromatin. Loss of MMSET expression alters adhesion properties, suppresses growth and induces apoptosis in MM cells. Consequently, genes affected by high levels of MMSET are implicated in the p53 pathway, cell cycle regulation and integrin signaling. Regulation of many of these genes required functional histone methyl-transferase (HMT) activity of MMSET. These results implicate MMSET as a major epigenetic regulator in t(4;14)+ MM.
2010-10-20 | GSE24746 | GEO
Project description:MMSET regulation of gene expression in t(4 14)+ myeloma
| PRJNA248290 | ENA
Project description:The MMSET (Multiple Myeloma SET domain) protein is overexpressed in multiple myeloma patients with the translocation t(4;14). Although studies have shown the involvement of MMSET/WHSC1 in development, its mode of action in the pathogenesis of multiple myeloma (MM) is largely unknown. We found that MMSET is a major regulator of chromatin structure and transcription in t(4;14) MM cells. High levels of MMSET correlate with an increase in lysine 36 methylation of histone H3 and a decrease in lysine 27 methylation across the genome, leading to a more open structural state of the chromatin. Loss of MMSET expression alters adhesion properties, suppresses growth and induces apoptosis in MM cells. Consequently, genes affected by high levels of MMSET are implicated in the p53 pathway, cell cycle regulation and integrin signaling. Regulation of many of these genes required functional histone methyl-transferase (HMT) activity of MMSET. These results implicate MMSET as a major epigenetic regulator in t(4;14)+ MM. Total RNA was isolated from two different systems: an inducible knock down designed in the 5' region of MMSET. Upon addition of doxycycline we block MMSET expression. The second system we used was a repletion system. By retroviral infection of knock out cells for MMSET we restored the expression of MMSET wild type and two mutants of the protein: one active and one catalytically inactive. Triplicates of each sample were analyzed.
2010-10-20 | E-GEOD-24746 | biostudies-arrayexpress
Project description:We investigated gene expression in isogenic myeloma cell lines with or without overexpressed MMSET protein. MMSET is a histone methyltransferase which methylates lysine 36 on histone H3. Overexpression of MMSET in myeloma leads to a global increase in H3K36 methylation and concomitant decrease in H3K27 methylation. These global changes in histone methylation lead to altered gene expression. Total RNA was extracted from parental KMS11 cell line, NTKO cells which have the wild type MMSET allele inactivated and TKO cells which have overexpressed MMSET allele inactivated. Two different TKO clones were tested. Each sample was analyzed in triplicate.
2014-09-01 | E-GEOD-57863 | biostudies-arrayexpress
Project description:CD86 regulates a pro-survival signal in myeloma cells
| PRJNA352410 | ENA
Project description:We investigated gene expression in isogenic myeloma cell lines with or without overexpressed MMSET protein. MMSET is a histone methyltransferase which methylates lysine 36 on histone H3. Overexpression of MMSET in myeloma leads to a global increase in H3K36 methylation and concomitant decrease in H3K27 methylation. These global changes in histone methylation lead to altered gene expression.
2014-09-01 | GSE57863 | GEO
Project description:Multiple myeloma (MM) is characterized by recurrent chromosomal translocations. The translocation t(4;14)(p16;q32) is one of the most common translocation in MMs, affecting 15% of patients, and is associated with very poor prognosis. The histone methyltransferase (HMTase) MMSET is universally overexpressed in t(4;14) MM as a result of the t(4;14) translocation. MMSET is capable of producing 3 major isoforms, the full length MMSET II, short isoforms REIIBP and MMSET I. MMSET II has been suggested to play an important tumorigenic role in t(4;14) MM, but little is yet known about whether and how the MMSET short isoforms contribute to MM tumorigenesis. The aim of this study is to characterize MMSET I roles and determine its downstream targets in t(4;14) MM. In t(4;14) MM cells MMSET I knockdown with shRNAs induced cell apoptosis, reduced colony formation and inhibited tumorigenicity in vivo. We also found MMSET I knockdown decreased GLO1 expression, and ectopic MMSET I increased GLO1 expression, suggesting that MMSET I is an upstream regulator of GLO1. Further analysis indicated that MMSET I bound to GLO1 promoter region and depended on its C-terminus to regulate GLO1 expression. Our preliminary data suggested that MMSET I is an oncoprotein and could regulate GLO1 expression in t(4;14) multiple myeloma cells.
2019-01-01 | GSE98433 | GEO
Project description:Multiple myeloma (MM) is a malignant B cell dyscrasia characterized by the accumulation of clonal plasma cells (PC) within the bone marrow. Epigenetic factors are involved in MM initiation, progression, and occurrence of chemoresistance. Among them EZH2, the Polycomb Repressive Complex 2 (PRC2) catalytic subunit and NSD2 (MMSET), the target oncogene of t(4;14) primary translocation, are both associated with poor prognosis values and contribute to MM disease. In this study, we identified a physical interaction between EZH2 and MMSET in MM. We used MMSET-depleted MM cells and MAK-683, an allosteric inhibitor of EZH2, to disrupt this interaction and understand its implication in MM biology and resistance to anti-MM drugs. Through its interaction with EZH2, MMSET regulates PRC2 nuclear localization in MM cells, promotes a particularly poor prognosis in MM patients, and modulates the expression of tumor-suppressor genes involved in p53 pathway. We also demonstrated that MAK-683 can interfere with this interaction and synergizes with conventional drugs used in MM treatment: Melphalan, an alkylating agent triggering DNA Damage Response (DDR); and Panobinostat, a Histone De-Acetylase (HDAC) inhibitor directedly regulating p53 acetylation and stability.
2024-08-09 | GSE242500 | GEO