Perspectives on Unidirectional versus Divergent Transcription

Duttke, Sascha H.; Lacadie, Scott A.; Ibrahim, Mahmoud M.; Glass, Christopher K.; Corcoran, David L.; Benner, Chris; Heinz, Sven; Kadonaga, James T.; Ohler, Uwe

doi:10.1016/j.molcel.2015.10.014

Cited by 22 publications

(26 citation statements)

References 11 publications

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“…3D). Thus, while the degree of bidirectionality can vary Duttke et al 2015b), we find that this variance is equivalent at enhancers and mRNA promoters containing stable PICs.…”

Section: Genome-wide Human Transcription Initiationmentioning

confidence: 73%

Genome-wide uniformity of human ‘open’ pre-initiation complexes

Lai

Pugh

2016

Genome Res.

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Transcription of protein-coding and noncoding DNA occurs pervasively throughout the mammalian genome. Their sites of initiation are generally inferred from transcript 5 ′ ends and are thought to be either locally dispersed or focused. How these two modes of initiation relate is unclear. Here, we apply permanganate treatment and chromatin immunoprecipitation (PIPseq) of initiation factors to identify the precise location of melted DNA separately associated with the preinitiation complex (PIC) and the adjacent paused complex (PC). This approach revealed the two known modes of transcription initiation. However, in contrast to prevailing views, they co-occurred within the same promoter region: initiation originating from a focused PIC, and broad nucleosome-linked initiation. PIP-seq allowed transcriptional orientation of Pol II to be determined, which may be useful near promoters where sufficient sense/anti-sense transcript mapping information is lacking. PIP-seq detected divergently oriented Pol II at both coding and noncoding promoters, as well as at enhancers. Their occupancy levels were not necessarily coupled in the two orientations. DNA sequence and shape analysis of initiation complex sites suggest that both sequence and shape contribute to specificity, but in a context-restricted manner. That is, initiation sites have the locally "best" initiator (INR) sequence and/or shape. These findings reveal a common core to pervasive Pol II initiation throughout the human genome.

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“…3D). Thus, while the degree of bidirectionality can vary Duttke et al 2015b), we find that this variance is equivalent at enhancers and mRNA promoters containing stable PICs.…”

Section: Genome-wide Human Transcription Initiationmentioning

confidence: 73%

Genome-wide uniformity of human ‘open’ pre-initiation complexes

Lai

Pugh

2016

Genome Res.

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“…The expression of these genes was shown to be sensitive to RNase H overexpression. Although the role of R-loop formation in antisense regulation is still unclear, available evidence shows that it may both up-and down-regulate the expression of certain antisense transcripts, and more interestingly, play a role in determining the direction of divergent gene transcription [52][53][54].…”

Section: The Genomic Distribution Of R-loopsmentioning

confidence: 99%

R-loop: an emerging regulator of chromatin dynamics

Al-Hadid

Yang

2016

ABBS

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The dynamic structure of chromatin, which exists in two conformational states: heterochromatin and euchromatin, alters the accessibility of the DNA to regulatory factors during transcription, replication, recombination, and DNA damage repair. Chemical modifications of histones and DNA, as well as adenosine triphospahate-dependent nucleosome remodeling, have been the major focus of research on chromatin dynamics over the past two decades. However, recent studies using a DNA-RNA hybrid-specific antibody and next-generation sequencing approaches have revealed that the formation of R-loops, one of the most common non-canonical DNA structures, is an emerging regulator of chromatin states. This review focuses on recent insights into the interplay between R-loop formation and the epigenetic modifications of chromatin in normal and disease states.

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“…In the absence of a critical vertebrate‐specific function for divergent transcription, it is hard to envision why separate reverse core promoters would be maintained at all human gene promoters. Yet, the existence of a substantial group of unidirectional human promoters has recently been called into question, mostly due to different assumptions for distinguishing background from significant start‐site signal in sequencing data . Interestingly, functional luciferase assays for a set of random human promoters (filtered for annotated bidirectional cases) suggested that 48% drive transcription in both directions and 48% drive transcription largely in one direction likely reflecting divergent and unidirectional promoters well before the genome‐wide discovery of promoter‐associated, unstable, upstream, antisense transcripts .…”

Section: Promoter Directionalitymentioning

confidence: 99%

“…Yet, the existence of a substantial group of unidirectional human promoters has recently Two mechanisms contributing to promoter directionality have been described, namely gene looping [38] and forward/reverse core promoter strength [6,33], both of which cooperate with, influence, and/or are influenced by chromatin state. been called into question, mostly due to different assumptions for distinguishing background from significant start-site signal in sequencing data [39,40]. Interestingly, functional luciferase assays for a set of random human promoters (filtered for annotated bidirectional cases) suggested that 48% drive transcription in both directions and 48% drive transcription largely in one direction [14] likely reflecting divergent and unidirectional promoters well before the genome-wide discovery of promoter-associated, unstable, upstream, antisense transcripts [15][16][17].…”

Section: Promoter Directionalitymentioning

confidence: 99%

“…Though histone modification types and quantities at promoters have been shown to be predictive of gene expression levels or promoter subclasses [42,43], it is common practice to consider signal within large windows around annotated, or experimentally measured, TSSs. Given the variation in transcriptional directionality from promoter regions [6,24,25,27,32,39] (Fig. 2) and its relationship with upstream histone PTMs (Fig.…”

Section: Directionally Resolving the Relationship Between Histone Modmentioning

confidence: 99%

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Divergent transcription and epigenetic directionality of human promoters

et al. 2016

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Genome‐wide datasets measuring nascent RNA have revealed that active human promoters frequently display divergent transcription, generating a stable mRNA in the forward direction toward the gene and a typically unstable one in the reverse direction away from the gene. Recent work has shown that these transcripts originate from two distinct core promoters within a single nucleosome‐free region (NFR). Different levels of forward and reverse activity lead to a wide range of directionality for promoter NFRs. Importantly, directionality is also reflected in the epigenetic modifications of nucleosomes immediately adjacent to the NFR. Here, we review the current literature pertaining to divergent transcription from promoter NFRs and its association with combinatorial histone post‐translational modifications, or chromatin states, on upstream and downstream nucleosomes. Finally, we discuss several models to interpret the directionality of promoter chromatin states.

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Perspectives on Unidirectional versus Divergent Transcription

Cited by 22 publications

References 11 publications

Genome-wide uniformity of human ‘open’ pre-initiation complexes

Genome-wide uniformity of human ‘open’ pre-initiation complexes

R-loop: an emerging regulator of chromatin dynamics

Divergent transcription and epigenetic directionality of human promoters

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