Chromatin Remodelling and RNA Processing

Böhm, Stefanie; Farrants, Ann‐Kristin Östlund

doi:10.5772/20998

Cited by 3 publications

(3 citation statements)

References 116 publications

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“…Promoter proximal pausing is known to be controlled by the negative regulators NELF and DSIF, whereas the C-terminal domain (CTD) of Pol II interacts with the capping components for 5 ′ -capping of the nascent mRNA. Similarly, polyadenylation and splicing are controlled by both the CTD of Pol II and correctly positioned nucleosomes (Böhm and Östlund Farrants 2011). Especially for the latter aspect, alternative splicing has been implicated to be regulated by alternative CTD phosphorylation regulated by the SWI/SNF chromatin remodeling complex (Batsché et al 2006), rich heptad repeat.…”

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confidence: 99%

Broad domains of histone marks in the highly compact Paramecium macronuclear genome

et al. 2022

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The unicellular ciliate Paramecium contains a large vegetative macronucleus with several unusual characteristics, including an extremely high coding density and high polyploidy. As macronculear chromatin is devoid of heterochromatin, our study characterizes the functional epigenomic organization necessary for gene regulation and proper Pol II activity. Histone marks (H3K4me3, H3K9ac, H3K27me3) reveal no narrow peaks but broad domains along gene bodies, whereas intergenic regions are devoid of nucleosomes. Our data implicate H3K4me3 levels inside ORFs to be the main factor associated with gene expression, and H3K27me3 appears in association with H3K4me3 in plastic genes. Silent and lowly expressed genes show low nucleosome occupancy, suggesting that gene inactivation does not involve increased nucleosome occupancy and chromatin condensation. Because of a high occupancy of Pol II along highly expressed ORFs, transcriptional elongation appears to be quite different from that of other species. This is supported by missing heptameric repeats in the C-terminal domain of Pol II and a divergent elongation system. Our data imply that unoccupied DNA is the default state, whereas gene activation requires nucleosome recruitment together with broad domains of H3K4me3. In summary, gene activation and silencing in Paramecium run counter to the current understanding of chromatin biology.

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confidence: 99%

Broad domains of histone marks in the highly compact Paramecium macronuclear genome

et al. 2022

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“…Promoter proximal pausing is known to be controlled by the negative regulators NELF and DSIF, while the C-terminal domain (CTD) of Pol II interacts with the capping components for 5capping of the nascent mRNA. Similarly, polyadenylation and splicing are controlled by both, the CTD of Pol II and correctly positioned nucleosomes [10]. Especially for the latter aspect, alternative splicing has been implicated to be regulated by alternative CTD phosphorylation regulated by the SWI/SNF chromatin remodeling complex [7].…”

Section: Introductionmentioning

confidence: 99%

Broad domains of histone marks in the highly compact Paramecium macronuclear genome

Drews

Salhab

Karunanithi

et al. 2021

Preprint

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The unicellular ciliate Paramecium contains a large vegetative macronucleus with several unusual characteristics including an extremely high coding density and high polyploidy. As macronculear chromatin is devoid of heterochromatin our study characterizes the functional epigenomic organisation necessary for gene regulation and proper PolII activity. Histone marks (H3K4me3, H3K9ac, H3K27me3) revealed no narrow peaks but broad domains along gene bodies, whereas intergenic regions were devoid of nucleosomes. Our data implicates H3K4me3 levels inside ORFs to be the main factor to associate with gene expression and H3K27me3 appears to occur as a bistable domain with H3K4me3 in plastic genes. Surprisingly, silent and lowly expressed genes show low nucleosome occupancy suggesting that gene inactivation does not involve increased nucleosome occupancy and chromatin condensation. Due to a high occupancy of Pol II along highly expressed ORFs, transcriptional elongation appears to be quite different to other species. This is supported by missing heptameric repeats in the C-terminal domain of Pol II and a divergent elongation system. Our data implies that unoccupied DNA is the default state, whereas gene activation requires nucleosome recruitment together with broad domains of H3K4me3. This could represent a buffer for paused Pol II along ORFs in absence of elongation factors of higher eukaryotes.

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“…In addition to its function in relaxing supercoiled DNA, cumulative evidence supports a direct role of TOP1 in transcriptional regulation. For example, during transcription, RNAPII pauses at initiation and splice sites [6] , while TOP1 has been proposed to hold RNAPII at the promoter-proximal pause site [7] . Nonetheless, the exact molecular mechanism by which TOP1 pauses RNAPII at the initiation site remains to be defined.…”

Section: Introductionmentioning

confidence: 99%

Topoisomerase I in Human Disease Pathogenesis and Treatments

Liu

2016

Genomics, Proteomics & Bioinformatics

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Mammalian topoisomerase 1 (TOP1) is an essential enzyme for normal development. TOP1 relaxes supercoiled DNA to remove helical constraints that can otherwise hinder DNA replication and transcription and thus block cell growth. Unfortunately, this exact activity can covalently trap TOP1 on the DNA that could lead to cell death or mutagenesis, a precursor for tumorigenesis. It is therefore important for cells to find a proper balance between the utilization of the TOP1 catalytic activity to maintain DNA topology and the risk of accumulating the toxic DNA damages due to TOP1 trapping that prevents normal cell growth. In an apparent contradiction to the negative attribute of the TOP1 activity to genome stability, the detrimental effect of the TOP1-induced DNA lesions on cell survival has made this enzyme a prime target for cancer therapies to kill fast-growing cancer cells. In addition, cumulative evidence supports a direct role of TOP1 in promoting transcriptional progression independent of its topoisomerase activity. The involvement of TOP1 in transcriptional regulation has recently become a focus in developing potential new treatments for a subtype of autism spectrum disorders. Clearly, the impact of TOP1 on human health is multifold. In this review, we will summarize our current understandings on how TOP1 contributes to human diseases and how its activity is targeted for disease treatments.

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Chromatin Remodelling and RNA Processing

Cited by 3 publications

References 116 publications

Broad domains of histone marks in the highly compact Paramecium macronuclear genome

Broad domains of histone marks in the highly compact Paramecium macronuclear genome

Broad domains of histone marks in the highly compact Paramecium macronuclear genome

Topoisomerase I in Human Disease Pathogenesis and Treatments

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