REDfly v3.0: toward a comprehensive database of transcriptional regulatory elements in Drosophila

Gallo, Steven M.; Gerrard, Dave T.; Miner, David; Simich, Michael; Soye, Benjamin J. Des; Bergman, Casey M.; Halfon, Marc S.

doi:10.1093/nar/gkq999

Cited by 160 publications

(221 citation statements)

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“…Given this, we next investigated the direct relationship between eRNA and enhancer activity during Drosophila embryogenesis, making use of the thousands of characterized developmental enhancers whose spatial and temporal activity has been assessed in vivo in transgenic embryos (Gallo et al 2011;Bonn et al 2012a;Kvon et al 2014). Both PRO-cap and CAGE signals were used as two independent measures of eRNA expression.…”

Section: Resultsmentioning

confidence: 99%

“…We first ranked enhancers-both in vivo characterized (Gallo et al 2011;Bonn et al 2012a;Kvon et al 2014) and predicted (Zinzen et al 2009)-by their levels of eRNA based on their nascent PRO-cap signal ( Fig. 3A; Supplemental Table S8).…”

Section: Highly Transcribed Developmental Enhancers Have Weak Promotementioning

confidence: 99%

“…Here, we exploited thousands of characterized developmental enhancers (Gallo et al 2011;Bonn et al 2012a;Kvon et al 2014) and putative enhancers defined by TF co-occupancy (Zinzen et al 2009;Junion et al 2012) available in Drosophila to characterize eRNA properties during embryogenesis using deeply sequenced PROcap (a precision nuclear run-on sequencing variant) and CAGE (cap analysis of gene expression) data. Our results reveal that active developmental enhancers possess a range of eRNA levels and directionality.…”

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The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription

et al. 2018

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Gene expression is regulated by promoters, which initiate transcription, and enhancers, which control their temporal and spatial activity. However, the discovery that mammalian enhancers also initiate transcription questions the inherent differences between enhancers and promoters. Here, we investigate the transcriptional properties of enhancers during Drosophila embryogenesis using characterized developmental enhancers. We show that while the timing of enhancer transcription is generally correlated with enhancer activity, the levels and directionality of transcription are highly varied among active enhancers. To assess how this impacts function, we developed a dual transgenic assay to simultaneously measure enhancer and promoter activities from a single element in the same embryo. Extensive transgenic analysis revealed a relationship between the direction of endogenous transcription and the ability to function as an enhancer or promoter in vivo, although enhancer RNA (eRNA) production and activity are not always strictly coupled. Some enhancers (mainly bidirectional) can act as weak promoters, producing overlapping spatio-temporal expression. Conversely, bidirectional promoters often act as strong enhancers, while unidirectional promoters generally cannot. The balance between enhancer and promoter activity is generally reflected in the levels and directionality of eRNA transcription and is likely an inherent sequence property of the elements themselves.

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Section: Resultsmentioning

confidence: 99%

Section: Highly Transcribed Developmental Enhancers Have Weak Promotementioning

confidence: 99%

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The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription

et al. 2018

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“…We then selected an additional 14 enhancers from the REDfly database of known Drosophila cis regulatory elements (Gallo et al 2011) (Table 1). We focused on enhancers that are active in stereotyped patterns across the developing ommatidial clusters of the third instar larval eye disc, reasoning that this tissue is generally permissive to transvection based on prior analyses (Leiserson et al 1994;Wu and Howe 1995;Bateman et al 2012a).…”

Section: Resultsmentioning

confidence: 99%

“…To generate piB-LTL-lacZ derivatives carrying different enhancers, potential target enhancers were identified using the REDFly database (Gallo et al 2011), and primers for amplifying enhancer sequences were either identified from a previous publication (Aerts et al 2010) or designed using Primer3 software (Untergasser et al 2012). Enhancer sequences were amplified via PCR from Drosophila genomic DNA and cloned into either pcr2.1 using a TOPO-TA cloning kit (Invitrogen) or pSC-A using a Strataclone PCR cloning kit (Agilent Technologies).…”

Section: Plasmid Construction and Transgenicsmentioning

confidence: 99%

The Capacity to Act in Trans Varies Among Drosophila Enhancers

Blick

Mayer-Hirshfeld

Malibiran³

et al. 2016

Genetics

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The interphase nucleus is organized such that genomic segments interact in cis, on the same chromosome, and in trans, between different chromosomes. In Drosophila and other Dipterans, extensive interactions are observed between homologous chromosomes, which can permit enhancers and promoters to communicate in trans. Enhancer action in trans has been observed for a handful of genes in Drosophila, but it is as yet unclear whether this is a general property of all enhancers or specific to a few. Here, we test a collection of well-characterized enhancers for the capacity to act in trans. Specifically, we tested 18 enhancers that are active in either the eye or wing disc of third instar Drosophila larvae and, using two different assays, found evidence that each enhancer can act in trans. However, the degree to which trans-action was supported varied greatly between enhancers. Quantitative analysis of enhancer activity supports a model wherein an enhancer's strength of transcriptional activation is a major determinant of its ability to act in trans, but that additional factors may also contribute to an enhancer's trans-activity. In sum, our data suggest that a capacity to activate a promoter on a paired chromosome is common among Drosophila enhancers.KEYWORDS RMCE; interchromosomal interactions; long-range enhancer; somatic homolog pairing; transvection T HE spatial organization of the interphase eukaryotic genome is characterized by extensive long-distance interactions between distal chromosome regions (Sanyal et al. 2012). Interactions have been identified between sequences on the same chromosome (in cis) or on different chromosomes (in trans) (Lieberman-Aiden et al. 2009;Duan et al. 2010;Sexton et al. 2012;van de Werken et al. 2012;Nagano et al. 2013;Zhang et al. 2013). Many long-distance interactions in cis underlie the activation of specific genes, and in some cases, sequences have been identified that facilitate interactions between a distal enhancer and a specific promoter target (Zhou and Levine 1999;Calhoun et al. 2002;Calhoun and Levine 2003;Lin 2003;Akbari et al. 2008;Fujioka et al. 2009;Majumder et al. 2015). In contrast, the genetic impacts of trans-interactions between chromosomes are less clearly understood. Examples of gene regulation involving interchromosomal associations have been described (Spilianakis et al. 2005;Bacher et al. 2006;Xu et al. 2006;Apostolou and Thanos 2008;Sandhu et al. 2009;Markenscoff-Papadimitriou et al. 2014;Patel et al. 2014), but it remains unclear whether it is common for sequences that regulate gene expression to communicate between different chromosomes when they are physically juxtaposed.In Drosophila melanogaster, extensive trans-interactions are observed between homologous chromosomes in virtually all somatic tissues, a phenomenon known as somatic homolog pairing (reviewed by McKee 2004;Bosco 2012). The close proximity of homologous chromosomes in Drosophila can permit an enhancer to act in trans on a promoter on the paired homolog, a form of pairing-dependent ...

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Evidence for a hierarchical transcriptional circuit in Drosophila male germline involving testis‐specific TAF and two gene‐specific transcription factors, Mod and Acj6

et al. 2017

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Edited by Lukas Alfons HuberTo analyze transcription factors involved in gene regulation by testis-specific TAF (tTAF), tTAF-dependent promoters were mapped and analyzed in silico. Core promoters show decreased AT content, paucity of classical promoter motifs, and enrichment with translation control element CAAAATTY. Scanning of putative regulatory regions for known position frequency matrices identified 19 transcription regulators possibly contributing to tTAF-driven gene expression. Decreased male fertility associated with mutation in one of the regulators, Acj6, indicates its involvement in male reproduction. Transcriptome study of testes from male mutants for tTAF, Acj6, and previously characterized tTAF-interacting factor Modulo implies the existence of a regulatory hierarchy of tTAF, Modulo and Acj6, in which Modulo and/or Acj6 regulate one-third of tTAF-dependent genes.Keywords: Drosophila; gene-specific transcription regulator; hierarchical transcriptional circuit; spermatogenesis; testis-specific TAF During Drosophila spermatogenesis, spermatogonial cells born from male germline stem cells multiply through four rounds of mitotic divisions and differentiate into spermatocytes. Upon lengthy maturation, spermatocytes in turn proceed through meiotic divisions to generate round haploid spermatids. Completion of the meiosis itself and dramatic morphological transformation of spermatids into mature sperms require numerous structural and regulatory proteins, expression of which is mostly supported by highly active transcription in spermatocytes [1]. The testisspecific gene expression is usually activated in spermatocytes [2]. Furthermore, a wealth of male-sterile mutants identified so far block at the initiation of spermatid differentiation program in spermatocytes [3]. Thus, the regulatory network in the spermatocyte period warrants detailed analysis both as a striking example of vast cell type-specific transcription and as a molecular mechanism that underlies male fertility.To date, very few transcription factors are known to be essential for spermatocyte-specific gene expression. The most well-characterized group includes genes of the meiotic arrest class, which encode either testis-specific TATA-binding protein-associated factors (tTAFs) or components of testis meiotic arrest complex (tMAC), except that Achintya and Vismay constitute a distinct complex [2]. The tMAC complex controls expression of key G2-M cell cycle genes [4], and its Abbreviations cTFIID, canonical TFIID; PFMs, position frequency matrices; TAF, TATA-binding protein associated factors; tBRD, testis-specific bromodomain protein; TCE, translational control element; tMAC, testis meiotic arrest complex; TSSs, transcription start sites; tTAF, testis-specific TAF. 46FEBS Letters 592 (2018) 46-59 ª 2017 Federation of European Biochemical Societies disruption shows dramatic drop in transcription of over 1500 genes in testes, whose effect is broader than the tTAF disruption [2]. The five tTAFs identified thus far in the primary spermatocytes are als...

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REDfly v3.0: toward a comprehensive database of transcriptional regulatory elements in Drosophila

Cited by 160 publications

References 10 publications

The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription

The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription

The Capacity to Act in Trans Varies Among Drosophila Enhancers

Evidence for a hierarchical transcriptional circuit in Drosophila male germline involving testis‐specific TAF and two gene‐specific transcription factors, Mod and Acj6

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