Genome-wide Identification and Characterization of Enhancers Across 10 Human Tissues

Xiong, Lili; Kang, Ran; Ding, Ruofan; Kang, Wenyuan; Zhang, Yiming; Liu, Wenrong; Huang, Qingqing; Ji, Meng; Guo, Zhiyun

doi:10.7150/ijbs.26605

Cited by 25 publications

(26 citation statements)

References 41 publications

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“…In general, enhancers direct lineage-specific transcriptional programs in a more predominant manner compared to promoters [56]. Around half of the enhancers identified in different tissues including brain, heart, ovaries, and placenta were tissue-specific [57]. Consistently, enhancers were the most distinctive identifying feature of tissue of origin upon analysis of hundreds of patient samples and human cell lines [58].…”

Section: Enhancers Are Context-specific and Indispensable To Cancer Cmentioning

confidence: 92%

Perturbing Enhancer Activity in Cancer Therapy

Hamdan

Johnsen

2019

Preprint

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Tight regulation of gene transcription is essential for normal development, tissue homeostasis and disease-free survival. Enhancers are distal regulatory elements in the genome that provide specificity to gene expression programs and are frequently misregulated in cancer. Recent studies examined various enhancer-driven malignant dependencies and identified different approaches to specifically target these programs. In this review, we describe numerous features that make enhancers good transcriptional targets in cancer therapy and discuss different approaches to overcome enhancer perturbation. Interestingly, a number of approved therapeutic agents such as cyclosporine, steroid hormones, and thiazolidinediones actually function by affecting enhancer landscapes by directly targeting very specific transcription factor programs. More recently, a broader approach to targeting deregulated enhancer programs has been achieved via Bromodomain and Extraterminal (BET) inhibition or perturbation of transcription-related cyclin-dependent kinases (CDK). One challenge to enhancer-targeted therapy is proper patient stratification. We suggest that monitoring of enhancer RNA (eRNA) expression may serve as a unique biomarker of enhancer activity that can help to predict and monitor responsiveness to enhancer-targeted therapies. A more thorough investigation of cancer-specific enhancers and the underlying mechanisms of deregulation will pave the road for an effective utilization of enhancer modulators in a precision oncology approach to cancer treatment.

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Section: Enhancers Are Context-specific and Indispensable To Cancer Cmentioning

confidence: 92%

Perturbing Enhancer Activity in Cancer Therapy

Hamdan

Johnsen

2019

Preprint

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“…Currently, non-coding transcription around genomic regulatory elements termed enhancers is a focus point within the field. Enhancers are gene-distal loci capable of regulating the transcription of target genes by increasing the recruitment of RNA polymerase II to target genes [48][49][50]. Enhancers are often (although not always) bi-directionally transcribed into 200+ nt lncRNA transcripts referred to as enhancer RNAs (eRNAs).…”

Section: Nucleosome Remodelersmentioning

confidence: 99%

Non-Coding RNAs and Nucleosome Remodeling Complexes: An Intricate Regulatory Relationship

Patty

Hainer

2020

Biology

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Eukaryotic genomes are pervasively transcribed, producing both coding and non-coding RNAs (ncRNAs). ncRNAs are diverse and a critical family of biological molecules, yet much remains unknown regarding their functions and mechanisms of regulation. ATP-dependent nucleosome remodeling complexes, in modifying chromatin structure, play an important role in transcriptional regulation. Recent findings show that ncRNAs regulate nucleosome remodeler activities at many levels and that ncRNAs are regulatory targets of nucleosome remodelers. Further, a series of recent screens indicate this network of regulatory interactions is more expansive than previously appreciated. Here, we discuss currently described regulatory interactions between ncRNAs and nucleosome remodelers and contextualize their biological functions.

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“…In general, enhancers direct lineage-specific transcriptional programs in a more predominant manner compared to promoters [63]. Around half of the enhancers identified in different tissues including brain, heart, ovaries, and placenta were tissue-specific [64]. Consistently, enhancers were the most distinctive identifying feature of tissue of origin upon analysis of hundreds of patient samples and human cell lines [65].…”

Section: Perturbing Enhancer Activity By Therapeutic Agents and Inmentioning

confidence: 99%

Perturbing Enhancer Activity in Cancer Therapy

Hamdan

Johnsen

2019

Cancers

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Tight regulation of gene transcription is essential for normal development, tissue homeostasis, and disease-free survival. Enhancers are distal regulatory elements in the genome that provide specificity to gene expression programs and are frequently misregulated in cancer. Recent studies examined various enhancer-driven malignant dependencies and identified different approaches to specifically target these programs. In this review, we describe numerous features that make enhancers good transcriptional targets in cancer therapy and discuss different approaches to overcome enhancer perturbation. Interestingly, a number of approved therapeutic agents, such as cyclosporine, steroid hormones, and thiazolidinediones, actually function by affecting enhancer landscapes by directly targeting very specific transcription factor programs. More recently, a broader approach to targeting deregulated enhancer programs has been achieved via Bromodomain and Extraterminal (BET) inhibition or perturbation of transcription-related cyclin-dependent kinases (CDK). One challenge to enhancer-targeted therapy is proper patient stratification. We suggest that monitoring of enhancer RNA (eRNA) expression may serve as a unique biomarker of enhancer activity that can help to predict and monitor responsiveness to enhancer-targeted therapies. A more thorough investigation of cancer-specific enhancers and the underlying mechanisms of deregulation will pave the road for an effective utilization of enhancer modulators in a precision oncology approach to cancer treatment.

show abstract

Genome-wide Identification and Characterization of Enhancers Across 10 Human Tissues

Cited by 25 publications

References 41 publications

Perturbing Enhancer Activity in Cancer Therapy

Perturbing Enhancer Activity in Cancer Therapy

Non-Coding RNAs and Nucleosome Remodeling Complexes: An Intricate Regulatory Relationship

Perturbing Enhancer Activity in Cancer Therapy

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