Browse
Submit Data
Databases
API
Help
Login

Dataset Information

0 Views

12 Connections

1 Citations

0 Reanalyses

0 Downloads

Omics score: 2

Identifying transcripts that are transcriptinoally regulated by CBFB and RUNX1 using RNAseq

ABSTRACT: Using RNAseq to identify differentially expressed transcripts between CBFB wild type (WT) and knockout (KO) or between RUNX1 wild type (WT) and knockout (KO) MCF10A cells. Overall design: Three repeats for CBFB KO and CBFB WT MCF10A cells. Four repeats for RUNX1 KO and RUNX1 WT MCF10A cells. One CBFB KO clone (#751) and two RUNX1 KO clones (5008 and 5010) were used.

INSTRUMENT(S): Illumina HiSeq 2500 (Homo sapiens)

ORGANISM(S): Homo sapiens

SUBMITTER: Jing Huang

PROVIDER: GSE120216 | GEO | 2019-04-18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

primary

			Action	DRS
	GSE120216_CBFB_KOvs_WT.csv.gz	Csv
	GSE120216_RUNX1_KO1vsWT.csv.gz	Csv
	GSE120216_RUNX1_KO2vsWT.csv.gz	Csv
	GSE120216_matrix_CBFB.xlsx	Xlsx
	GSE120216_matrix_RUNX1.xlsx	Xlsx

Items per page:

1 - 5 of 5

Publications

The transcription factor CBFB suppresses breast cancer through orchestrating translation and transcription.

Malik Navdeep N Yan Hualong H Moshkovich Nellie N Palangat Murali M Yang Howard H Sanchez Vanesa V Cai Zhuo Z Peat Tyler J TJ Jiang Shunlin S Liu Chengyu C Lee Maxwell M Mock Beverly A BA Yuspa Stuart H SH Larson Daniel D Wakefield Lalage M LM Huang Jing J

Nature communications 20190506 1

Translation and transcription are frequently dysregulated in cancer. These two processes are generally regulated by distinct sets of factors. The CBFB gene, which encodes a transcription factor, has recently emerged as a highly mutated driver in a variety of human cancers including breast cancer. Here we report a noncanonical role of CBFB in translation regulation. RNA immunoprecipitation followed by deep sequencing (RIP-seq) reveals that cytoplasmic CBFB binds to hundreds of transcripts and reg ...[more]

PMID: 31061501

Similar Datasets

Cbfb/Runx1 repression-independent blockage of differentiation and accumulation of Csf2rb-expressing cells by Cbfb-MYH11.

Project description:It is known that CBFB-MYH11, the fusion gene generated by inversion of chromosome 16 in human acute myeloid leukemia, is causative for oncogenic transformation. However, the mechanism by which CBFB-MYH11 initiates leukemogenesis is not clear. Previously published reports showed that CBFB-MYH11 dominantly inhibits RUNX1 and CBFB, and such inhibition has been suggested as the mechanism for leukemogenesis. Here we show that Cbfb-MYH11 caused Cbfb/Runx1 repression-independent defects in both primitive and definitive hematopoiesis. During primitive hematopoiesis, Cbfb-MYH11 delayed differentiation characterized by sustained expression of Gata2, Il1rl1, and Csf2rb, a phenotype not found in Cbfb and Runx1 knockout mice. Expression of Cbfb-MYH11 in the bone marrow induced the accumulation of abnormal progenitor-like cells expressing Csf2rb in preleukemic mice. The expression of all 3 genes was detected in most human and murine CBFB-MYH11(+) leukemia samples. Interestingly, Cbfb-MYH11(+) preleukemic progenitors and leukemia-initiating cells did not express Csf2rb, although the majority of leukemia cells in our Cbfb-MYH11 knockin mice were Csf2rb(+). Therefore Csf2rb can be used as a negative selection marker to enrich preleukemic progenitor cells and leukemia-initiating cells from Cbfb-MYH11 mice. These results suggest that Cbfb/Runx1 repression-independent activities contribute to leukemogenesis by Cbfb-MYH11.

2010-01-01 | S-EPMC2826765 | BioStudies

Autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells.

Project description:Although runt-related transcription factor 1 (RUNX1) and its associating core binding factor-? (CBFB) play pivotal roles in leukemogenesis, and inhibition of RUNX1 has now been widely recognized as a novel strategy for anti-leukemic therapies, it has been elusive how leukemic cells could acquire the serious resistance against RUNX1-inhibition therapies and also whether CBFB could participate in this process. Here, we show evidence that p53 (TP53) and CBFB are sequentially up-regulated in response to RUNX1 depletion, and their mutual interaction causes the physiological resistance against chemotherapy for acute myeloid leukemia (AML) cells. Mechanistically, p53 induced by RUNX1 gene silencing directly binds to CBFB promoter and stimulates its transcription as well as its translation, which in turn acts as a platform for the stabilization of RUNX1, thereby creating a compensative RUNX1-p53-CBFB feedback loop. Indeed, AML cells derived from relapsed cases exhibited higher CBFB expression levels compared to those from primary AML cells at diagnosis, and these CBFB expressions were positively correlated to those of p53. Our present results underscore the importance of RUNX1-p53-CBFB regulatory loop in the development and/or maintenance of AML cells, which could be targeted at any sides of this triangle in strategizing anti-leukemia therapies.

2017-01-01 | S-EPMC5709397 | BioStudies

Runx1 is required for hematopoietic defects and leukemogenesis in Cbfb-MYH11 knock-in mice.

Project description:CBF?-SMMHC (core-binding factor ?-smooth muscle myosin heavy chain), the fusion protein generated by the chromosome 16 inversion fusion gene, CBFB-MYH11, is known to initiate leukemogenesis. However, the mechanism through which CBF?-SMMHC contributes to leukemia development is not well understood. Previously, it was proposed that CBF?-SMMHC acts by dominantly repressing the transcription factor RUNX1 (Runt-related protein 1), but we recently showed that CBF?-SMMHC has activities that are independent of RUNX1 repression. In addition, we showed that a modified CBF?-SMMHC with decreased RUNX1-binding activity accelerates leukemogenesis. These results raise questions about the importance of RUNX1 in leukemogenesis by CBF?-SMMHC. To test this, we generated mice expressing Cbfb-MYH11 in a Runx1-deficient background, resulting from either homozygous Runx1-null alleles (Runx1(-/-)) or a single dominant-negative Runx1 allele (Runx1(+/lz)). We found that loss of Runx1 activity rescued the differentiation defects induced by Cbfb-MYH11 during primitive hematopoiesis. During definitive hematopoiesis, RUNX1 loss also significantly reduced the proliferation and differentiation defects induced by Cbfb-MYH11. Importantly, Cbfb-MYH11-induced leukemia had much longer latency in Runx1(+/lz) mice than in Runx1-sufficient mice. These data indicate that Runx1 activity is critical for Cbfb-MYH11-induced hematopoietic defects and leukemogenesis.

2015-01-01 | S-EPMC4526349 | BioStudies

Chd7 deficiency delays leukemogenesis in mice induced by Cbfb-MYH11.

Project description:Inversion of chromosome 16 is a consistent finding in patients with acute myeloid leukemia subtype M4 with eosinophilia, which generates a CBFB-MYH11 fusion gene. Previous studies showed that the interaction between CBF?-smooth muscle myosin heavy chain (SMMHC; encoded by CBFB-MYH11) and RUNX1 plays a critical role in the pathogenesis of this leukemia. Recently, it was shown that chromodomain helicase DNA-binding protein-7 (CHD7) interacts with RUNX1 and suppresses RUNX1-induced expansion of hematopoietic stem and progenitor cells. These results suggest that CHD7 is also critical for CBFB-MYH11-induced leukemogenesis. To test this hypothesis, we generated Chd7f/fMx1-CreCbfb+/56M mice, which expressed the Cbfb-MYH11 fusion gene and deactivated Chd7 in hematopoietic cells upon inducing Cre with polyinosinic-polycytidylic acid. The Lin-Sca1-c-Kit+ (LK) population was significantly lower in Chd7f/fMx1-CreCbfb+/56M mice than in Mx1-CreCbfb+/56M mice. In addition, there were fewer 5-bromo-2'-deoxyuridine-positive cells in the LK population in Chd7f/fMx1-CreCbfb+/56M mice, and genes associated with cell cycle, cell growth, and proliferation were differentially expressed between Chd7f/fMx1-CreCbfb+/56M and Mx1-CreCbfb+/56M leukemic cells. In vitro studies showed that CHD7 interacted with CBF?-SMMHC through RUNX1 and that CHD7 enhanced transcriptional activity of RUNX1 and CBF?-SMMHC on Csf1r, a RUNX1 target gene. Moreover, RNA sequencing of c-Kit+ cells showed that CHD7 functions mostly through altering the expression of RUNX1 target genes. Most importantly, Chd7 deficiency delayed Cbfb-MYH11-induced leukemia in both primary and transplanted mice. These data indicate that Chd7 is important for Cbfb-MYH11-induced leukemogenesis by facilitating RUNX1 regulation of transcription and cellular proliferation.

2017-01-01 | S-EPMC5709785 | BioStudies

The transcription factor CBFB suppresses breast cancer through orchestrating translation and transcription.

Project description:Translation and transcription are frequently dysregulated in cancer. These two processes are generally regulated by distinct sets of factors. The CBFB gene, which encodes a transcription factor, has recently emerged as a highly mutated driver in a variety of human cancers including breast cancer. Here we report a noncanonical role of CBFB in translation regulation. RNA immunoprecipitation followed by deep sequencing (RIP-seq) reveals that cytoplasmic CBFB binds to hundreds of transcripts and regulates their translation. CBFB binds to mRNAs via hnRNPK and enhances translation through eIF4B, a general translation initiation factor. Interestingly, the RUNX1 mRNA, which encodes the transcriptional partner of CBFB, is bound and translationally regulated by CBFB. Furthermore, nuclear CBFB/RUNX1 complex transcriptionally represses the oncogenic NOTCH signaling pathway in breast cancer. Thus, our data reveal an unexpected function of CBFB in translation regulation and propose that breast cancer cells evade translation and transcription surveillance simultaneously through downregulating CBFB.

2019-01-01 | S-EPMC6502810 | BioStudies

Anterior cleft palate due to Cbfb deficiency and its rescue by folic acid.

Project description:Core binding factor ? (Cbfb) is a cofactor of the Runx family of transcription factors. Among these transcription factors, Runx1 is a prerequisite for anterior-specific palatal fusion. It was previously unclear, however, whether Cbfb served as a modulator or as an obligatory factor in the Runx signaling process that regulates palatogenesis. Here, we report that Cbfb is essential and indispensable in mouse anterior palatogenesis. Palatal fusion in Cbfb mutants is disrupted owing to failed disintegration of the fusing epithelium specifically at the anterior portion, as observed in Runx1 mutants. In these mutants, expression of TGFB3 is disrupted in the area of failed palatal fusion, in which phosphorylation of Stat3 is also affected. TGFB3 protein has been shown to rescue palatal fusion in vitro TGFB3 also activated Stat3 phosphorylation. Strikingly, the anterior cleft palate in Cbfb mutants is further rescued by pharmaceutical application of folic acid, which activates suppressed Stat3 phosphorylation and Tgfb3 expression in vitro With these findings, we provide the first evidence that Cbfb is a prerequisite for anterior palatogenesis and acts as an obligatory cofactor in the Runx1/Cbfb-Stat3-Tgfb3 signaling axis. Furthermore, the rescue of the mutant cleft palate using folic acid might highlight potential therapeutic targets aimed at Stat3 modification for the prevention and pharmaceutical intervention of cleft palate.

2019-01-01 | S-EPMC6602316 | BioStudies

RNA binding of CBFB and hnRNPK

Project description:RNA immunoprecipitation assay followed by next generation sequencing (RIPseq) to identify RNAs bound by CBFB and hnRNPK in breast cells. Overall design: One repeat for RIPseq of CBFB and two repeats for hnRNPK. A stable cell line derived from MCF10A cells (ATCC, Cat: CRL-10317) expressing FLAG tagged CBFB was used for CBFB RIP using the FLAG antibody (Sigma, Cat: A2220). Parental MCF10A cells were used for hnRNPK RIP using hnRNPK antibody (Bethyl Laboratory, Cat: A300-674A).

2019-04-18 | GSE119800 | GEO

Gata2 deficiency delays leukemogenesis while contributing to aggressive leukemia phenotype in Cbfb-MYH11 knockin mice.

Project description:Inversion of chromosome 16 (inv(16)) generates a fusion gene CBFB-MYH11, which is a driver mutation for acute myeloid leukemia (AML). Gene expression profiling suggests that Gata2, a hematopoietic transcription factor, is a top upregulated gene in preleukemic Cbfb-MYH11 knockin mice and is expressed in human inv(16) AML. On the other hand, we have also identified recurrent monoallelic deletions of GATA2 in relapsed human CBF-AML patients. To clarify the role of Gata2 in leukemogenesis by Cbfb-MYH11, we generated conditional Cbfb-MYH11 knockin mice with Gata2 heterozygous knockout. Gata2 heterozygous knockout reduced abnormal myeloid progenitors, which are capable of inducing leukemia in the Cbfb-MYH11 mice. Consequently, Cbfb-MYH11 mice with Gata2 heterozygous knockout developed leukemia with longer latencies than those with intact Gata2. Interestingly, leukemic cells with Gata2 heterozygous knockout gained higher number of mutations and showed more aggressive phenotype in both primary and transplanted mice. Moreover, leukemic cells with Gata2 heterozygous knockout showed higher repopulating capacity in competitive transplantation experiments. In summary, reduction of Gata2 activity affects mutational dynamics of leukemia with delayed leukemia onset in Cbfb-MYH11 knockin mice, but paradoxically results in a more aggressive leukemia phenotype, which may be correlated with leukemia relapse or poor prognosis in human patients.

2020-01-01 | S-EPMC7056539 | BioStudies

CBFb Stabilizes HIV Vif to Counteract APOBEC3 at the Expense of RUNX1 Target Gene Expression [gene expression]

Project description:The HIV-1 accessory protein Vif hijacks a cellular Cullin-RING ubiquitin ligase, CRL5, to promote degradation of the APOBEC3 (A3) family of restriction factors. Recently, the cellular transcription cofactor CBFb was shown to form a complex with CRL5-Vif and to be essential for A3 degradation and viral infectivity. We now demonstrate that CBFb is required for assembling a well-ordered CRL5-Vif complex by inhibiting Vif oligomerization and by activating CRL5-Vif via direct interaction. The CRL5-Vif-CBFb holoenzyme forms a wellde?ned heterohexamer, indicating that Vif simultaneously hijacks CRL5 and CBFb. Heterodimers of CBFb and RUNX transcription factors contribute toward the regulation of genes, including those with immune system functions. We show that binding of Vif to CBFb is mutually exclusive with RUNX heterodimerization and impacts the expression of genes whose regulatory domains are associated with RUNX1. Our results provide a mechanism by which a pathogen with limited coding capacity uses one factor to hijack multiple host pathways. Analysis of Vif-dependent effects on gene expression in Jurkats when cells are activated for 4 or 6 hours with PMA and PHA

2013-01-17 | E-GEOD-42574 | BioStudies

Transcription profiling of mouse Cbfb-deficient regulatory T cells

Project description:Gene expression profiles of Cbfb-deficient and control Treg cells were compared. Abstract: Naturally arising regulatory T (Treg) cells express the transcription factor FoxP3, which critically controls the development and function of Treg cells. FoxP3 interacts with another transcription factor Runx1 (also known as AML1). Here we showed that Treg cell-specific deficiency of Cbfβ, a cofactor for all Runx proteins, or that of Runx1, but not Runx3, induced lymphoproliferation, autoimmune disease, and hyper-production of IgE. Cbfb-deleted Treg cells exhibited impaired suppressive function in vitro and in vivo, with altered gene expression profiles including attenuated expression of FoxP3 and high expression of interleukin-4. The Runx complex bound to more than 3000 gene loci in Treg cells, including the Foxp3 regulatory regions and the Il4 silencer. In addition, knockdown of RUNX1 showed that RUNX1 is required for the optimal regulation of FoxP3 expression in human T cells. Taken together, our results indicate that the Runx1-Cbfβ heterodimer is indispensable for in vivo Treg cell function, in particular, suppressive activity and optimal expression of FoxP3. Experiment Overall Design: CD4+CD25hi cells, most of which were Foxp3+ Treg cells, were isolated from Cbfb-flox/flox: Foxp3-ires-Cre (n = 3) and control Cbfb-flox/wt: Foxp3-ires-Cre (n = 3) mice. Total RNA was extracted from those purified Cbfb-deficient or control Treg cells.

2009-09-25 | E-GEOD-18148 | ArrayExpress