Comprehensive nucleosome mapping of the human genome in cancer progression

Druliner, Brooke R.; Vera, Daniel; Johnson, Ruth A.; Ruan, Xiaoyang; Apone, Lynne; Dimalanta, Eileen T.; Stewart, Fiona; Boardman, Lisa A.; Dennis, Jane A

doi:10.1101/021618

Cited by 3 publications

(4 citation statements)

References 57 publications

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“…KSHV is a human herpesvirus and the etiological agent of three human cancers [ 15 - 17 ]. Like other herpesviruses, KSHV exhibits two alternative life cycles, a quiescent latent stage and a productive lytic stage, both of which are crucial for KSHV pathogenesis [ 18 , 19 ]. We have made use of the iSLK.219 cell culture system, because it displays tight control of KSHV latency, but can be efficiently induced by doxycycline to undergo KSHV lytic reactivation [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Hierarchical regulation of the genome: global changes in nucleosome organization potentiate genome response

et al. 2016

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Nucleosome occupancy is critically important in regulating access to the eukaryotic genome. Few studies in human cells have measured genome-wide nucleosome distributions at high temporal resolution during a response to a common stimulus. We measured nucleosome distributions at high temporal resolution following Kaposi's-sarcoma-associated herpesvirus (KSHV) reactivation using our newly developed mTSS-seq technology, which maps nucleosome distribution at the transcription start sites (TSS) of all human genes. Nucleosomes underwent widespread changes in organization 24 hours after KSHV reactivation and returned to their basal nucleosomal architecture 48 hours after KSHV reactivation. The widespread changes consisted of an indiscriminate remodeling event resulting in the loss of nucleosome rotational phasing signals. Additionally, one in six TSSs in the human genome possessed nucleosomes that are translationally remodeled. 72% of the loci with translationally remodeled nucleosomes have nucleosomes that moved to positions encoded by the underlying DNA sequence. Finally we demonstrated that these widespread alterations in nucleosomal architecture potentiated regulatory factor binding. These descriptions of nucleosomal architecture changes provide a new framework for understanding the role of chromatin in the genomic response, and have allowed us to propose a hierarchical model for chromatin-based regulation of genome response.

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Section: Introductionmentioning

confidence: 99%

Hierarchical regulation of the genome: global changes in nucleosome organization potentiate genome response

et al. 2016

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“…H3K27ac ChIP-Seq fastq files PC3, LNCaP and PrEC cell lines were downloaded from GEO GSE57498, GSE73785, GSE57498, respectively [53,55]. Bowtie2 [56] were then used to map the fastq file to hg19 human genome reference.…”

Section: Identification Of H3k27ac Chip-seq Peak Regionsmentioning

confidence: 99%

An Integrative Analysis of Chromatin Interactions, Gene Expression and Genomic Variants Identifies 30 Likely Regulatory Variants in Prostate Cancer

Labani¹,

Beheshti²,

Argha³

et al. 2023

Preprint

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Prostate cancer (PC) is the most frequently diagnosed non-skin cancer in the world. Previous studies showed that genomic alterations represent the most common mechanism for molecular alterations that cause the development and progression of PC. Great efforts have been done to identify common protein-coding genetic variations; however, the impact of non-coding variations including regulatory genetic variants is not still well understood. To gain an understanding of the functional impact of genetic variants, particularly, regulatory variants in PC, we developed an integrative pipeline (AGV) that used whole genome/exome sequences, GWAS SNPs, chromosome conformation capture data, and ChIP-Seq signals to investigate the potential impact of genomic variants on the underlying target genes in PC. We identified 646 putative regulatory variants, of which 30 of them significantly altered the expression of at least one protein-coding gene. Our analysis of chromatin interactions data (Hi-C) revealed that the 30 putative regulatory variants may affect 131 coding and non-coding genes. Interestingly, our study showed the 131 protein-coding genes are involved in disease-related pathways including Reactome and MSigDB in which for most of them targeted treatment options are currently available. Together, our results provide a comprehensive map of genomic variants in PC and revealed their potential contribution to prostate cancer progression and development.

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“…These polyps were categorized into two groups: cancer-adjacent polyps (CAPs), derived from patients with colon adenocarcinoma and cancer free polyps (CFPs), derived from patients with no observed malignant tumors. We used our MNase-Transcription Start Site Sequence Capture method (mTSS-seq) established previously to produce high-resolution maps of lung adenocarcinoma (9) and colorectal carcinoma (10). Our mTSS-seq combines in-solution targeted enrichment of two kilobases centered on the transcription start sites of 21,857 human open reading frames (NCBI RefSeq).…”

Section: Nucleosome Distribution Is Invariant Between Cancer-free And...mentioning

confidence: 99%

“…Over the past several decades extensive research has been done to further understand the relationship between epigenetics and the development of cancer. These studies have determined factors that are implicated in cancer including DNA methylation, histone modifications, chromatin remodelers, and most recently, our work on nucleosome distribution alterations in early cancer (9,10). We have previously shown that nucleosome distribution is an early, widespread transformation event in lung and colon adenocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

Nucleosome sensitivity distinguishes colon polyps based on their transformation status

Khadem

Kossick

Fedyshyn

et al. 2022

Preprint

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One of the keys to eliminating the personal and financial costs of cancer lies in the early detection of the disease. Consequently, effective cancer interventions increasingly rely on our understanding of the earliest cellular and nuclear events that lead to oncogenic transformation. Colorectal cancer, the third most prevalent cancer in the United States, results from the transformation of polyps. Our group demonstrated that the alteration of chromatin organization is a pivotal event in this oncogenic transformation. Here, we analyze the differences of the nucleosomal sensitivity to mocroccocal nuclease (MNase) between histopathologically matched pre-cancerous polyps taken from patients that did not develop cancer (cancer-free polyps, CFP) and those that did develop cancer (cancer-associated polyps, CAP). We produced high-resolution nucleosome distribution and nucleosome sensitivity maps from each of the five CFP patient samples and three CAP patient samples. We show that nucleosome distribution is largely invariant between CFP and CAP samples. Nucleosome sensitivity, however, is a powerful analysis that can identify genomic locations that distinguish CFP from CAP. We have identified more than 1000 genomic locations with altered nucleosomal sensitivity that discriminate between CAP and CFP. Furthermore, we show that these genomic locations with altered nucleosomal sensitivity between CFP and CAP include genes that play critical roles in oncogenic transformation. We propose that nucleosome sensitivity serves as a robust biomarker indicating the oncogenic potential of precancerous polyps and could be used for the early detection of polyps that will become cancerous.

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Comprehensive nucleosome mapping of the human genome in cancer progression

Cited by 3 publications

References 57 publications

Hierarchical regulation of the genome: global changes in nucleosome organization potentiate genome response

Hierarchical regulation of the genome: global changes in nucleosome organization potentiate genome response

An Integrative Analysis of Chromatin Interactions, Gene Expression and Genomic Variants Identifies 30 Likely Regulatory Variants in Prostate Cancer

Nucleosome sensitivity distinguishes colon polyps based on their transformation status

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