Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Mechanisms of Ikaros Tumor Suppression with HDAC1 through distinct histone markers in Pre-B ALL Leukemia

ABSTRACT: Ikaros functions as a master regulator of lymphocyte differentiation and a tumor suppressor. Ikaros binds DNA and regulates gene expression by chromatin remodeling. Mechanisms of Ikaros-mediated tumor suppression are unknown. Here we examined genome-wide occupancy of Ikaros and histone deacetylase 1 (HDAC1) and Histone midificaition markers in human leukemia, and found that the Ikaros and HDAC1 showed similar binding partern and HDAC1âDNA interactions are associated with the presence of bivalent chromatin, and the recruitment of HDAC1 by Ikaros is associated with bivalent chromatin at Ikaros target genes. Examine the genome-wide binding of Ikaros, HDAC1, H3K9me3, H3K9ac, H3K27me3, H3K4me3 and H3K36me3 in Nalm6 ALL leukemia cells.

ORGANISM(S): Homo sapiens

SUBMITTER: chunhua song

PROVIDER: E-GEOD-44217 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Targeting casein kinase II restores Ikaros tumor suppressor activity and demonstrates therapeutic efficacy in high-risk leukemia.

Song Chunhua C Gowda Chandrika C Pan Xiaokang X Ding Yali Y Tong Yongqing Y Tan Bi-Hua BH Wang Haijun H Muthusami Sunil S Ge Zheng Z Sachdev Mansi M Amin Shantu G SG Desai Dhimant D Gowda Krishne K Gowda Raghavendra R Robertson Gavin P GP Schjerven Hilde H Muschen Markus M Payne Kimberly J KJ Dovat Sinisa S

Blood 20150728 15

Ikaros (IKZF1) is a tumor suppressor that binds DNA and regulates expression of its target genes. The mechanism of Ikaros activity as a tumor suppressor and the regulation of Ikaros function in leukemia are unknown. Here, we demonstrate that Ikaros controls cellular proliferation by repressing expression of genes that promote cell cycle progression and the phosphatidylinositol-3 kinase (PI3K) pathway. We show that Ikaros function is impaired by the pro-oncogenic casein kinase II (CK2), and that ...[more]

PMID: 26219304

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Project description:Analysis of transcriptional regulation in human cells has implicated a large number of promoter-specific DNA-binding proteins that regulate transcription via diverse mechanisms. In some cases, these DNA-sequence-specific factors associate with intermediaries that orchestrate interactions with the chromatin-modifying enzymes. One such intermediary is HCF-1 (host-cell factor-1; HCFC1). HCF-1, first identified for its involvement in herpes-simplex virus transcription and subsequently shown to be an important cell-cycle regulator, has a poorly defined role in genome-wide transcriptional regulation. We show here, by chromatin immunoprecipitation followed by high-throughput sequence analysis (ChIP-seq), that HCF-1 is a major transcriptional start site associated factor, whose promoter association correlates positively with transcriptional activity. Thus, in HeLa cells HCF-1 is observed on 5400 generally active CpG-island promoters. Examination of the DNA sequences underlying the HCF-1-binding sites revealed three sequence motifs associated with the binding of (i) ZNF143 and Ronin/THAP11, (ii) GABP, and (iii) YY1 sequence-specific transcription factors. Subsequent ChIP-seq analysis of these four transcription factors revealed a large co-association of HCF-1 with these four transcription factors at approximately 90% of HCF-1-bound promoters. These studies suggest that a relatively small number of transcription factors -- some (ZNF143 and Ronin/THAP11) in novel combinations -- play a major role in HeLa-cell transcriptional regulation in association with HCF-1. This experiment includes the sequencing data of material obtained from chromatin immunoprecipitation using antibodies against HCFC1(antibodies against the C-subunit and the N-subunit), PolII(antibody against the RPB2 subunit), H3K36ME3 and H3K4Me3 histone modifications, ZNF143, THAP11, GABPalpha and YY1. It also includes control data of the Input material. All of them were done using HeLa cycling cells.

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Dataset Information

Mechanisms of Ikaros Tumor Suppression with HDAC1 through distinct histone markers in Pre-B ALL Leukemia

Publications

Targeting casein kinase II restores Ikaros tumor suppressor activity and demonstrates therapeutic efficacy in high-risk leukemia.

Similar Datasets

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