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Genome wide analysis of cis-regulatory elements reveals gene regulatory networks in metabolic adaptation of cavefish

ABSTRACT: Genome wide analysis of cis-regulatory elements reveals gene regulatory networks in metabolic adaptation of cavefish

PROVIDER: PRJNA641362 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12074700.fastq.gz	Fastqsanger.gz
	SRR12074701.fastq.gz	Fastqsanger.gz
	SRR12074702.fastq.gz	Fastqsanger.gz
	SRR12074703.fastq.gz	Fastqsanger.gz
	SRR12074704.fastq.gz	Fastqsanger.gz

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Effects of cis-regulatory elements on proteome

Project description:Background Genomic variations contribute to the phenotypic diversity of individuals. A number of polymorphisms in protein-coding regions that alter drug efficacy or lead to adverse reactions have been characterized; however, noncoding regions that affect drug responses are largely overlooked, except for a limited number of well-studied enhancers. Results We conducted a quantitative assessment of cis-regulatory elements (CREs) based on transcription initiation profiling of mRNAs and noncoding RNAs, including enhancer RNAs, by using CAGE (Cap Analysis of Gene Expression). Candidate CREs identified in a hepatocellular carcinoma HepG2 cell line with stable expression of drug-responsive transcription factor pregnane X receptor (PXR) were further narrowed down by integrating data of PXR-binding sites in human primary hepatocytes and genome-wide association studies. We found more than 100-fold enrichments of the candidates to genetically associated loci with circulating levels of bilirubin and vitamin D, which implicated a link to adverse reactions of PXR ligands. We uncovered novel enhancers of UGT1A1 and TSKU through CRISPR/Cas9 knockout experiments. We identified alleles altering regulatory activities of UGT1A1 and CYP24A1enhancers by using luciferase reporter assay. Furthermore, our siRNA experiments revealed an unexpected impact of TSKU on the expression of vitamin D-metabolizing enzymes. Conclusions Our transcriptome-based assessment of CREs expanded the list of drug-inducible and PXR-mediated enhancers and super-enhancers. We identified regulatory alleles that alter drug-induced gene expressions, and discovered a novel molecular cascade associated with an adverse reaction. Our results contribute a precise understanding of the noncoding elements of the human genome underlying drug responses.

2025-04-17 | PXD060446 | Pride

Predictable Engineering of Signal-Dependent Cis-Regulatory Elements

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Genome wide analysis of cis-regulatory elements reveals gene regulatory networks in metabolic adaptation of cavefish

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Characterizing cis-regulatory elements associated with mammary gland function

Project description:The goal of this study is to improve the quality, efficiency, and sustainability of milk production by improving the understanding of the function of cis-regulatory elements in regulating the bovine mammary gland. To this end, we have characterized the non-lactating and lactating mammary gland transcriptomes by whole transcriptome shotgun sequencing (RNA-seq). We will identify cis-regulatory elements in the non-lactating and lactating bovine mammary gland genome-wide. Finally, we will annotate and characterize mammary gland cis-regulatory elements by computational analysis and identify high-resolution genome-wide in vivo footprints of diverse trans-acting-factors (TF), over-represented TF bindings sites and overlapping SNPs.

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