ChIP-seq of circadian transcription factors in MLL-AF9 leukemia cell lines
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE70686 | GEO | 2016/01/01
SECONDARY ACCESSION(S): PRJNA289353
REPOSITORIES: GEO
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Project description:We performed ChIP-seq of two core circadian TFs which were found to be important in leukemia proliferation, in order to identify potential target genes regulated by the circadian rhythm. Here, we performed ChIP-seq for the core circadian transcription factors CLOCK and ARNTL (BMAL1) in NOMO-1 and THP-1 cells.
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2024-09-20 | E-MTAB-13457 | biostudies-arrayexpress
Project description:Using larval zebrafish as a model system, we applied a genome-wide transcriptome approach that allowed us to investigate circadian gene expression that can be associated with various tissues and cell types. Our analysis of circadian gene regulatory network revealed a general principle: circadian clock controls diverse aspects of circadian physiology through transcriptional cascade of transcription factors (TFs). As a proof of this principle, we focused on microphthalmia-associated transcription factor a (mitfa), a dark-induced TF controlling melanogenesis in melanocytes. We demonstrated experimentally that there is a circadian rhythm of melanin synthesis mediated by mitfa. The circadian rhythm of mitfa is in turn driven by both endogenous clock and external light/dark cycle. The circadian rhythm of melanin synthesis may play an important role in zebrafishM-bM-^@M-^Ys adaptation to daily cycle of lighting condition in the environment. Total RNA of larval sample was extracted using Trizol (Invitrogen) according to the manufacturerM-bM-^@M-^Ys instruction. The quantity and quality of the RNA samples were assessed with a NanoDrop ND-1000 spectrometer (NanoDrop Technologies) and an Agilent 2100 bioanalyzer (Agilent). 12 LD RNA samples and 12 DD RNA samples were used for Agilent whole zebrafish 4x44K microarray, which contains 43,603 probes for a whole-genome transcriptional profile. Morpholinos oligonucleotides (MOs) were purchased from Gene Tools. All MOs except standard control were designed to target the start codon region of the genes. MOs were used at the following final doses: clock MO, 2.5 ng; mitfa MO, 9 ng or 13ng (microarray analysis). MOs were pressure-injected into 1- to 2-cell stage embryos at a volume of 1nl using Picospritzer II injectors as previously described (Janik et al. 2000). Each MO sample contained 40 individually treated larvae. Then the sample are collected and microarray are conducted just as before.
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Project description:Epigenetic regulations play crucial roles in leukemogenesis and leukemia progression. SUV39H1 is the dominant H3K9 methyltransferase in the hematopoietic system, and its expression declines with aging. However, the role of SUV39H1 via its-mediated repressive modification H3K9me3 in leukemogenesis/leukemia progression remains to be explored. We found that SUV39H1 was down-regulated in a variety of leukemias, including MLL-r AML, as compared with normal individuals. Decreased levels of Suv39h1 expression and genomic H3K9me3 occupancy were observed in LSCs from MLL-r-induced AML mouse models in comparison with that of hematopoietic stem/progenitor cells. Suv39h1 overexpression increased leukemia latency and decreased the frequency of LSCs in MLL-r AML mouse models, while Suv39h1 knockdown accelerated disease progression with increased number of LSCs. Increased Suv39h1 expression led to the inactivation of Hoxb13 and Six1, as well as reversion of Hoxa9/Meis1 downstream target genes, which in turn decelerated leukemia progression. Interestingly, Hoxb13 expression is up-regulated in MLL-AF9-induced AML cells, while knockdown of Hoxb13 in MLL-AF9 leukemic cells significantly prolonged the survival of leukemic mice with reduced LSC frequencies. Our data revealed that SUV39H1 functions as a tumor suppressor in MLL-AF9-induced AML progression. These findings provide the direct link of SUV39H1 to AML development and progression.
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Project description:Sleep has been strongly implicated in learning and especially in the reprocessing of recently acquired memory. Children with intellectual disability (ID) tend to have sleep-wake disturbances, which may contribute to the pathophysiology of the disease. As far as sleep is, in part, a circadian process, we decided to study rhythmic gene expression in hippocampus, a brain structure, which plays a key role in memory in human and rodents. By investigating the transcriptome of mouse adult hippocampus, we report here the identification of 663 circadian rhythm (CR)-regulated genes, which have been clustered in four categories, based on their temporal pattern of expression. In addition to the standard core-clock genes, enrichment analysis of the hippocampal CR-regulated genes revealed the presence of several transcription factors, underlying the existence of an inter-regulation of genes' expression between clusters. Interestingly, these hippocampal circadian rhythm-regulated genes are very enriched in sleep/wakefulness related genes. We show here that glucocorticoid signaling, already shown to be involved in memory regulation, is a circadian regulated pathway in hippocampus. Furthermore, we identified a list of 30 CR-regulated ID genes. Our results demonstrate that hippocampus can be considered as a peripheral oscillator and illustrate the link between circadian rhythm, sleep, intellectual disability and memory consolidation. In order to identify circadian rhythm-regulated genes in mouse hippocampus, we realized a study in dark-dark conditions, thus allowing to overcome the effects induced by light changes. To systematically identify genes with circadian regulated expression, RNA samples from the hippocampus of three mice at four Circadian Time (CT) points were used for expression profiling using Agilent microarray technology. The dark/dark period started at 7 p.m. The Circadian Time (CT) 18 samples were taken after 30 h of continuous dark; the other circadian times followed at 6-h intervals: CT0, CT6 and CT12 after 36, 42 and 48 h of continuous darkness, respectively.
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