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ZC3H4 restricts non-coding transcription in human cells

ABSTRACT: ZC3H4 restricts non-coding transcription in human cells

PROVIDER: PRJNA684332 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13239424.fastq.gz	Fastqsanger.gz
	SRR13239425.fastq.gz	Fastqsanger.gz
	SRR13239426.fastq.gz	Fastqsanger.gz
	SRR13239427.fastq.gz	Fastqsanger.gz
	SRR13239428.fastq.gz	Fastqsanger.gz

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ZC3H4 restricts non-coding transcription in human cells

Project description:The human genome encodes many thousands of non-coding RNAs. A majority of these are curtailed by early transcriptional termination followed by rapid degradation. The mechanisms and factors responsible for restricting non-coding transcription in this fashion are poorly characterised, but these RNAs vastly outnumbering those with coding potential. We identify ZC3H4 as a metazoan-specific factor controlling the level and extent of hundreds of unstable transcripts. The most striking effects are for antisense RNAs and those transcribed from super-enhancers, but a subset of protein-coding RNAs are also affected. ZC3H4 occupies these genomic loci and its level of recruitment correlates with RNA extension observed in its absence. Finally, engineered targeting of ZC3H4 to an otherwise unaffected RNA supresses its production and leads to rapid degradation, endowing it with the features associated with its natural targets. We conclude that ZC3H4 is a hitherto uncharacterised factor that restricts unproductive transcription.

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ZC3H4 restricts non-coding transcription in human cells.

Project description:The human genome encodes thousands of non-coding RNAs. Many of these terminate early and are then rapidly degraded, but how their transcription is restricted is poorly understood. In a screen for protein-coding gene transcriptional termination factors, we identified ZC3H4. Its depletion causes upregulation and extension of hundreds of unstable transcripts, particularly antisense RNAs and those transcribed from so-called super-enhancers. These loci are occupied by ZC3H4, suggesting that it directly functions in their transcription. Consistently, engineered tethering of ZC3H4 to reporter RNA promotes its degradation by the exosome. ZC3H4 is predominantly metazoan -interesting when considering its impact on enhancer RNAs that are less prominent in single-celled organisms. Finally, ZC3H4 loss causes a substantial reduction in cell proliferation, highlighting its overall importance. In summary, we identify ZC3H4 as playing an important role in restricting non-coding transcription in multicellular organisms.

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Hda1C restricts burst frequency to limit divergent non-coding transcription

Project description:We used Native Elongation Transcript sequencing (NET-seq) to investigate the genome-wide effect of the Hda1 histone deacetylase complex (Hda1C) on the repression of divergent non-coding (DNC) transcription at bidirectional promoters in yeast S.cerevisiae.

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Natural Selection has Shaped Coding and Non-coding Transcription in Primate CD4+ T-cells

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The pause-initiation limit restricts transcription activation in human cells

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Natural Selection has Shaped Coding and Non-coding Transcription in Primate CD4+ T-cells

Project description:Transcriptional regulatory changes have been shown to contribute to phenotypic differences between species, but many questions remain about how gene expression evolves. Here we report the first comparative study of nascent transcription in primates. We used PRO-seq to map actively transcribing RNA polymerases in resting and activated CD4+ T-cells in multiple human, chimpanzee, and rhesus macaque individuals, with rodents as outgroups. This approach allowed us to directly measure active transcription separately from post-transcriptional processes. We observed general conservation in coding and non-coding transcription, punctuated by numerous differences between species, particularly at distal enhancers and non-coding RNAs. Transcription factor binding sites are a primary determinant of transcriptional differences between species. We found evidence for stabilizing selection on gene expression levels and adaptive substitutions associated with lineage-specific transcription. Finally, rates of evolutionary change are strongly correlated with long-range chromatin interactions. These observations clarify the role of primary transcription in regulatory evolution.

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