An ancient transcriptional regulatory linkage

Rebeiz, Mark; Stone, Tammie; Posakony, James W.

doi:10.1016/j.ydbio.2005.03.004

Cited by 51 publications

(27 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…N, N box, CACNAG (Oellers et al 1994); EB, class B E box, CACGTG (Dang et al 1992); EC, Hairy site/class C E box, CACGCG (Rebeiz et al 2005). The numbers of D. melanogaster sites that are conserved in each of eight other Drosophila species were identified in BLAT readouts and individual species sequence data.…”

Section: Resultsmentioning

confidence: 99%

Phylogenetic Footprinting Analysis in the Upstream Regulatory Regions of the DrosophilaEnhancer of splitGenes

et al. 2007

View full text Add to dashboard Cite

During Drosophila development Suppressor of Hairless ½Su(H)-dependent Notch activation upregulates transcription of the Enhancer of split-Complex ½E(spl)-C genes. Drosophila melanogaster E(spl) genes share common transcription regulators including binding sites for Su(H), proneural, and E(spl) basic-helix-loophelix (bHLH) proteins. However, the expression patterns of E(spl) genes during development suggest that additional factors are involved. To better understand regulators responsible for these expression patterns, recently available sequence and annotation data for multiple Drosophila genomes were used to compare the E(spl) upstream regulatory regions from more than nine Drosophila species. The mg and mb regulatory regions are the most conserved of the bHLH genes. Fine analysis of Su(H) sites showed that high-affinity Su(H) paired sites and the Su(H) paired site plus proneural site (SPS 1 A) architecture are completely conserved in a subset of Drosophila E(spl) genes. The SPS 1 A module is also present in the upstream regulatory regions of the more ancient mosquito and honeybee E(spl) bHLH genes. Additional transcription factor binding sites were identified upstream of the E(spl) genes and compared between species of Drosophila. Conserved sites provide new understandings about E(spl) regulation during development. Conserved novel sequences found upstream of multiple E(spl) genes may play a role in the expression of these genes.

show abstract

Section: Resultsmentioning

confidence: 99%

Phylogenetic Footprinting Analysis in the Upstream Regulatory Regions of the DrosophilaEnhancer of splitGenes

et al. 2007

View full text Add to dashboard Cite

show abstract

“…In the SCORE analysis, binding sites for Hes-class bHLH repressor proteins (R sites) were identified by searching with the motif definition CACGYG (32). R sites identified in neur fit the more restricted definition GGCACGYGHY (33), with allowance for a one-base mismatch at any of the four positions flanking the hexamer core. Binding sites for the Senseless (Sens) protein (L sites) were identified by searching with the motif definition AAATCWSW (34).…”

Section: Methodsmentioning

confidence: 99%

Neural precursor-specific expression of multiple Drosophila genes is driven by dual enhancer modules with overlapping function

Miller

Rebeiz

Atanasov

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Transcriptional cis-regulatory modules (CRMs), or enhancers, are responsible for directing gene expression in specific territories and cell types during development. In some instances, the same gene may be served by two or more enhancers with similar specificities. Here we show that the utilization of dual, or "shadow", enhancers is a common feature of genes that are active specifically in neural precursor (NP) cells in Drosophila. By genome-wide computational discovery of statistically significant clusters of binding motifs for both proneural activator (P) proteins and basic helix-loop-helix (bHLH) repressor (R) factors (a "P+R" regulatory code), we have identified NP-specific enhancer modules associated with multiple genes expressed in this cell type. These CRMs are distinct from those previously identified for the corresponding gene, establishing the existence of a dual-enhancer arrangement in which both modules reside close to the gene they serve. Using wild-type and mutant reporter gene constructs in vivo, we show that P sites in these modules mediate activation by proneural factors in "proneural cluster" territories, whereas R sites mediate repression by bHLH repressors, which serves to restrict expression specifically to NP cells. To our knowledge, our results identify the first direct targets of these bHLH repressors. Finally, using genomic rescue constructs for neuralized (neur), we demonstrate that each of the gene's two NP-specific enhancers is sufficient to rescue neur function in the lateral inhibition process by which adult sensory organ precursor (SOP) cells are specified, but that deletion of both enhancers results in failure of this event.neural precursors | dual enhancer modules | cis-regulatory code | proneural proteins | bHLH repressors S pecification of neural precursor (NP) cell fates is a core step in the process of neural development, and there has long been intense interest in its mechanistic basis. Among the most heavily investigated questions in this arena is how NP-specific expression of key regulatory factors associated with the NP fate is achieved. For example, multiple prior studies have used computational methods to identify NP-specific cis-regulatory modules (CRMs) genome-wide, in an attempt to define common transcription factor inputs that might underlie NP-specific gene expression (1-3).Proneural transcriptional activators of the basic helix-loophelix (bHLH) family are the top-level regulators of NP specification. They confer on cells in ectodermal tissue the potential to adopt the NP fate; loss of proneural gene function results in loss of all NPs and thus loss of expression of all NP-specific regulatory factors. However, proneural factors are not expressed only in NPs; rather, they are initially expressed in small groups of cells called proneural clusters (PNCs). At this stage of the process, most or all cells in the cluster have the potential to become an NP. This is prevented by "lateral inhibition", in which the single NP that will ultimately arise from the PNC inhibits al...

show abstract

“…Atoh1 is a member of the ancient family of bHLH transcription factors (Jones, 2004;Rebeiz et al, 2005). Multiple studies in other systems, in particular Drosophila nervous system, have established specific inhibitory interactions between bHLH molecules and several other signaling pathways.…”

Section: Id and Notch Signaling Act To Limit Atoh1 Expression And Haimentioning

confidence: 99%

Cellular commitment and differentiation in the organ of Corti

Kelley¹

2007

Int. J. Dev. Biol.

View full text Add to dashboard Cite

The organ of Corti, the sensory epithelium of the mammalian cochlea, develops from a subset of cells located along the dorsal side (referred to as the floor) of the cochlear duct. Over the course of embryonic development, cells within the developing organ of Corti become committed to develop as each of the unique cell types within the organ, including inner and outer hair cells, and at least four different types of supporting cells. Moreover, these different cell types are subsequently arranged into a highly rigorous cellular mosaic that includes the formation of ordered rows of both hair cells and supporting cells. The events that regulate both the location of the organ of Corti within the cochlear duct, the specification of each cell type and cellular patterning remain poorly understood. However, recent results have significantly improved our understanding of the molecular, genetic and cellular factors that mediate some of the decisions required for the development of this structure. In this review I will present an overview of cochlear development and then discuss some of the most recent and enlightening results regarding the molecular mechanism underlying the formation of this remarkable structure.

show abstract

An ancient transcriptional regulatory linkage

Cited by 51 publications

References 52 publications

Phylogenetic Footprinting Analysis in the Upstream Regulatory Regions of the DrosophilaEnhancer of splitGenes

Phylogenetic Footprinting Analysis in the Upstream Regulatory Regions of the DrosophilaEnhancer of splitGenes

Neural precursor-specific expression of multiple Drosophila genes is driven by dual enhancer modules with overlapping function

Cellular commitment and differentiation in the organ of Corti

Contact Info

Product

Resources

About