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Regulation of alternative polyadenylation by the C2H2-zinc finger protein Sp1

ABSTRACT: Regulation of alternative polyadenylation by the C2H2-zinc finger protein Sp1

PROVIDER: PRJNA697864 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13573500.fastq.gz	Fastqsanger.gz
	SRR13573501.fastq.gz	Fastqsanger.gz
	SRR13573502.fastq.gz	Fastqsanger.gz
	SRR13577207.fastq.gz	Fastqsanger.gz
	SRR13577207_1.fastq.gz	Fastqsanger.gz

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Regulation of alternative polyadenylation by the C2H2-zinc finger protein Sp1 [RNA-Seq]

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Regulation of alternative polyadenylation by the C2H2-zinc finger protein Sp1 [ChIP-Seq]

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Regulation of alternative polyadenylation by the C2H2-zinc finger protein Sp1 [CLIP-seq]

Project description:About 70% of human genes carry multiple polyadenylation signals, and mRNA 3’end formation is dynamically regulated under different physiological conditions. Global 3’end shortening through alternative polyadenylation (APA) correlates with enhanced cellular proliferation, and 3’ untranslated region (UTR) shortening is a widespread phenomenon in tumour cells, where it appears to enhance tumorigenic properties. However, the mechanisms responsible for this dynamic APA regulation remain incompletely understood. Here we show that transcription factor Sp1 binds directly to RNA in vivo and is a common repressor of distal poly (A) site usage. RNA-sequencing (RNA-seq) analysis identified 2344 genes (36% of total mapped mRNA transcripts) with lengthened 3’UTRs upon Sp1 depletion. Sp1 preferentially binds in vivo within the 3’UTRs of many of these lengthened transcripts and inhibits cleavage at distal sites by interacting physically with subunits of the core cleavage and polyadenylation (CPA) machinery. The 3’UTR lengths of Sp1 target genes in breast cancer patient RNA-seq data correlate with Sp1 expression levels, implicating Sp1-mediated APA regulation in modulating tumorigenic properties. Taken together, our findings reveal an important mechanism for dynamic APA regulation by unraveling a novel function of Sp1.

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Multiparameter functional diversity of human C2H2 zinc finger proteins [RNA-Seq]

Project description:C2H2 zinc finger proteins represent the largest and most enigmatic class of human transcription factors. Their C2H2 arrays are highly variable, indicating that most will have unique DNA binding motifs. However, most of the binding motifs have not been directly determined. We have determined the binding sites and motifs of 119 C2H2 zinc finger proteins and the expression pattern of 80 cell lines overexpressing C2H2 zinc finger proteins in order to study the role of C2H2 zinc finger proteins in gene regulation. We expressed GFP-tagged C2H2-ZF proteins in stable transgenic HEK293 cells. Total RNA was isolated using Trizol and sequencing libraries were constructed using TruSeq Stranded Total RNA Library Prep Kit with Ribo-Zero Gold or TruSeq RNA Library Preparation Kit v2.

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