Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape

O’Malley, Ronan; Huang, S.; Song, Lina; Lewsey, Mathew G.; Bartlett, Anna; Nery, Joseph R.; Galli, Mary; Gallavotti, Andrea; Ecker, Joseph R.

doi:10.1016/j.cell.2016.08.063

Cited by 354 publications

(499 citation statements)

References 47 publications

(59 reference statements)

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“…However, such a transcription factor would be unique for genes transcribed by RNA polymerase II in that it only functions when downstream of the transcription start site, and activates transcription several hundred nucleotides upstream of its binding site. The TTNGATYTG motif most closely resembles consensus sites for the GATA family of transcription factors [41,42], but GATA factor-binding sites do not meet the strict positional requirements characteristic of IME [43–45]. A second possible DNA-based model might include effects on local chromatin structure that favor transcript initiation, but this would not explain why these sequences must be downstream of the TSS to stimulate expression.…”

Section: Discussionmentioning

confidence: 99%

Intron-mediated enhancement is not limited to introns

Gallegos

Rose

2018

Preprint

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Certain introns strongly increase mRNA accumulation by a poorly understood mechanism known as Intron-Mediated Enhancement (IME). Introns that boost expression by IME have no effect when located upstream of or more than ~1 Kb downstream from the start of transcription. The sequence TTNGATYTG, which is over-represented in promoter-proximal introns in Arabidopsis thaliana, can convert a non-stimulating intron into one that strongly increases mRNA accumulation. We tested the ability of an intron containing this motif to stimulate expression from different locations and found that it had the same positional requirements as naturally occurring IME introns. The motif also stimulated gene expression from within the 5’-UTR and coding sequences of an intronless construct. Furthermore, the 5’-UTR of another gene increased expression when inserted into an otherwise non-stimulating intron in coding sequences. These results demonstrate that splicing is not required for intron-mediated enhancement, and suggest that other sequences downstream of the transcription start site in addition to introns may stimulate expression by a similar mechanism.

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Section: Discussionmentioning

confidence: 99%

Intron-mediated enhancement is not limited to introns

Gallegos

Rose

2018

Preprint

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“…These position-weight matrices (PWM, downloaded from the CisBP database) match consensus binding sequences previously determined with in vitro selection for SPLs [44] and TCP4 [39]. These targeted scans complement a wider analysis done with the 'Find Individual Occurences of Motifs' tool (FIMO) tool [45] and three collections of A. thaliana TF PWMs [43,46,47] documented in the supplemental materials [35]. An example sequence logo for one model, for SPL11, is shown in Figure 2A.…”

Section: Multiple Spls and Tcps Bind The Ago7 Promotermentioning

confidence: 98%

“…Data processing was done with the R Statistical Computing Environment [81] and the Bioconductor BioStrings package was used for PWM scans [82,83]. The relevant data supplement [35] also includes results from 'Find Individual Occurences of Motifs' tool (FIMO) scans [45] done via the online MEME Suite [84] version 4.12.0, with default settings (p < 10 −4 cutoff) and three collections of DNA-binding specificity models [43,46,47].…”

Section: Data and Code Availabilitymentioning

confidence: 99%

Functional dissection of theARGONAUTE7promoter

Hoyer

Pruneda‐Paz

Breton

et al. 2018

Preprint

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ARGONAUTES are the central effector proteins of RNA silencing which bind target transcripts in a small RNA-guided manner. Arabidopsis thaliana has ten ARGONAUTE (AGO) genes, with specialized roles in RNA-directed DNA methylation, post-transcriptional gene silencing, and antiviral defense. To better understand specialization among AGO genes at the level of transcriptional regulation we tested a library of 1497 transcription factors for binding to the promoters of AGO1, AGO10, and AGO7 using yeast 1-hybrid assays. A ranked list of candidate DNA-binding TFs revealed binding of the AGO7 promoter by a number of proteins in two families: the miR156-regulated SPL family and the miR319-regulated TCP family, both of which have roles in developmental timing and leaf morphology. Possible functions for SPL and TCP binding are unclear: we showed that these binding sites are not required for the polar expression pattern of AGO7, nor for the function of AGO7 in leaf shape. Normal AGO7 transcription levels and function appear to depend instead on an adjacent 124-bp region. Progress in understanding the structure of this promoter may aid efforts to understand how the conserved AGO7-triggered TAS3 pathway functions in timing and polarity.A total of 1497 TFs were tested for AGO promoter binding. This collection consisted mainly of 2/25 3/25 Figure 2. Identification of SPL11 binding sites. A. Sequence logo for SPL11 PWM, as downloaded from CisBP. Individual position weights can be interpreted as binding specificity contributions (changes in free energy, arbitrary units). B and C. Scores for SPL11 PWM at each position of the 1 kb region upstream of the annotated AGO7 transcription start site. D. Reporter activity (relative luminescence units normalized by A600) for SPL11 and pDEST22 (empty vector) tested in yeast against AGO7 promoter baits including several derivatives of the -531/-446 region. Modifications included one or two 4-bp deletions, 8 substitutions (TCCG/AAGG), and an unrelated 6-bp deletion; see Table 2, below. 4/25 6/25 8/25 Our truncation analysis provided preliminary evidence for two other functional regions of the AGO7 10/25 12/25 13/25

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“…De novo motif discovery of DAP‐seq peaks reported motifs consistent with those from ChIP‐seq and PBM methods, and unlike PBM or SELEX that uses synthetic DNA libraries, the peaks from DAP‐seq directly provide genomic coordinates of binding events in the genome without the need for motif scanning. Applying DAP‐seq to an Arabidopsis TF clone collection identified binding motifs for 549 TFs and high quality genome‐wide binding profiles for 349 TFs . Comparison of DAP‐seq and ChIP‐seq peaks showed that integrating DAP‐seq identified binding events with accessible chromatin filter resulted in more accurate prediction of in vivo binding compared to motif scanning …”

mentioning

confidence: 99%

“…Applying DAP‐seq to an Arabidopsis TF clone collection identified binding motifs for 549 TFs and high quality genome‐wide binding profiles for 349 TFs . Comparison of DAP‐seq and ChIP‐seq peaks showed that integrating DAP‐seq identified binding events with accessible chromatin filter resulted in more accurate prediction of in vivo binding compared to motif scanning …”

mentioning

confidence: 99%

Piecing together cis‐regulatory networks: insights from epigenomics studies in plants

Huang

Ecker

2017

WIREs Mechanisms of Disease

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5-Methylcytosine, a chemical modification of DNA, is a covalent modification found in the genomes of both plants and animals. Epigenetic inheritance of phenotypes mediated by DNA methylation is well established in plants. Most of the known mechanisms of establishing, maintaining and modifying DNA methylation have been worked out in the reference plant Arabidopsis thaliana. Major functions of DNA methylation in plants include regulation of gene expression and silencing of transposable elements (TEs) and repetitive sequences, both of which have parallels in mammalian biology, involve interaction with the transcriptional machinery, and may have profound effects on the regulatory networks in the cell. Methylome and transcriptome dynamics have been investigated in development and environmental responses in Arabidopsis and agriculturally and ecologically important plants, revealing the interdependent relationship among genomic context, methylation patterns, and expression of TE and protein coding genes. Analyses of methylome variation among plant natural populations and species have begun to quantify the extent of genetic control of methylome variation vs. true epimutation, and model the evolutionary forces driving methylome evolution in both short and long time scales. The ability of DNA methylation to positively or negatively modulate binding affinity of transcription factors (TFs) provides a natural link from genome sequence and methylation changes to transcription. Technologies that allow systematic determination of methylation sensitivities of TFs, in native genomic and methylation context without confounding factors such as histone modifications, will provide baseline datasets for building cell-type- and individual-specific regulatory networks that underlie the establishment and inheritance of complex traits. This article is categorized under: Laboratory Methods and Technologies > Genetic/Genomic Methods Biological Mechanisms > Regulatory Biology.

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Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape

Cited by 354 publications

References 47 publications

Intron-mediated enhancement is not limited to introns

Intron-mediated enhancement is not limited to introns

Functional dissection of theARGONAUTE7promoter

Piecing together cis‐regulatory networks: insights from epigenomics studies in plants

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