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LINE1 elements at Distal Junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells [UMI-4C]

ABSTRACT: LINE1 elements at Distal Junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells [UMI-4C]

PROVIDER: PRJNA1118225 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29234439.fastq.gz	Fastqsanger.gz
	SRR29234440.fastq.gz	Fastqsanger.gz
	SRR29234441.fastq.gz	Fastqsanger.gz
	SRR29234442.fastq.gz	Fastqsanger.gz
	SRR29234443.fastq.gz	Fastqsanger.gz

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LINE1 elements at Distal Junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells [UMI-4C]

Project description:In this study, we constructed UMI-4C profiles of 5 different genomic loci (viewpoints) in two H9 human hES cell lines - naïve and primed - in order to study the 3D chromatin contact maps of these selected loci.

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LINE1 elements at Distal Junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells [RNA-seq]

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LINE1 elements at Distal Junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells [ATAC-seq]

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LINE1 elements at Distal Junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells [RNA-seq]

Project description:LINE1 elements at Distal Junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells [RNA-seq]

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LINE1 elements at Distal Junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells [ATAC-seq]

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LINE1 and PRC2 control nucleolar organization and repression of the 8C-state in human ESCs

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Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation

Project description:Induction of DNA double-strand breaks (DSBs) in ribosomal DNA (rDNA) repeats is associated with ATM-dependent repression of ribosomal RNA synthesis and large-scale reorganization of nucleolar architecture, but the signaling events that regulate these responses are largely elusive. Here we show that the nucleolar response to rDNA breaks is dependent on both ATM and ATR activity. We further demonstrate that ATM- and NBS1-dependent recruitment of TOPBP1 in the nucleoli is required for inhibition of ribosomal RNA synthesis and nucleolar segregation in response to rDNA breaks. Mechanistically, TOPBP1 recruitment is mediated by phosphorylation-dependent interactions between three of its BRCT domains and conserved phosphorylated Ser/Thr residues at the C-terminus of the nucleolar phosphoprotein Treacle. Our data thus reveal an important cooperation between TOPBP1 and Treacle in the signaling cascade that triggers transcriptional inhibition and nucleolar segregation in response to rDNA breaks.

2019-12-06 | PXD015138 | Pride

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Project description:Nucleolar ribosomal DNA (rDNA) repeats control ribosome manufacturing. rDNA harbors a ribosomal RNA (rRNA) gene and an intergenic spacer (IGS). RNA polymerase (Pol) I transcribes rRNA genes yielding the rRNA components of ribosomes. Pol II at the IGS induces rRNA production by preventing Pol I from excessively synthesizing IGS non-coding RNAs (ncRNAs) that can disrupt nucleoli. At the IGS, Pol II regulatory processes and whether Pol I function can be beneficial remain unknown. Here, we identify IGS Pol II regulators, uncovering nucleolar optimization via IGS Pol I. Compartment-enriched proximity-dependent biotin identification (compBioID) showed enrichment of the TATA-less promoter-binding TBPL1 and transcription regulator PAF1 with IGS Pol II. TBPL1 localizes to TCT motifs, driving Pol II and Pol I and maintaining its baseline ncRNA levels. PAF1 promotes Pol II elongation, preventing unscheduled R-loops that hyper-restrain IGS Pol I and its ncRNAs. PAF1 or TBPL1 deficiency disrupts nucleolar organization and rRNA biogenesis. In PAF1-deficient cells, repressing unscheduled IGS R-loops rescues nucleolar organization and rRNA production. Depleting IGS Pol I-dependent ncRNAs is sufficient to compromise nucleoli. We present the interactome of nucleolar Pol II and show its control by TBPL1 and PAF1 ensures IGS Pol I ncRNAs maintaining nucleolar structure and operation.

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