Enhancer-PRE communication contributes to the expansion of gene expression domains in proliferating primordia

Abstract

the homeodomain proteins Engrailed (En) and Invected are expressed in the posterior (P) compartment, where they are required to repress Ci expression (Eaton and Kornberg, 1990) and relieve Ci-mediated repression of hh (Bejarano and Milan, 2009). PcG proteins help to maintain the repression of hh expression in A cells whereas TrxG proteins contribute to maintaining the expression of hh in P cells (Bejarano and Milan, 2009;Chanas and Maschat, 2005). Notch activity at the dorsal-ventral (DV) compartment boundary has also been reported to participate in the regulation of hh expression; however, the mechanistic basis behind this is uncertain (Bejarano and Milan, 2009). Although communication between the hh-ME and those cis-enhancers that integrate positional information conferred by the activities of Ci, En and Notch has been proposed as a way to initiate and maintain the transcriptional state of hh in P cells, the identity of these enhancers and the proposed communication remain elusive.Here, we have isolated a 4.3-kb cis-regulatory region that recapitulates hh expression in the P compartment of the wing primordium. This fragment includes the previously defined hh-ME and a nearby enhancer (termed C enhancer) that responds to En, Ci and Notch and drives gene expression to a thin stripe in the P compartment that corresponds to the DV compartment boundary. We present evidence that the ME maintains the initial transcriptional Development 138, 3125-3134 (2011) SUMMARYTrithorax-group and Polycomb-group proteins interact with chromosomal elements, termed PRE/TREs, to ensure stable heritable maintenance of the transcriptional state of nearby genes. Regulatory elements that bind both groups of proteins are termed maintenance elements (MEs). Some of these MEs maintain the initial activated transcriptional state of a nearby reporter gene through several rounds of mitosis during development. Here, we show that expression of hedgehog in the posterior compartment of the Drosophila wing results from the communication between a previously defined ME and a nearby cisregulatory element termed the C enhancer. The C enhancer integrates the activities of the Notch and Hedgehog signalling pathways and, from the early wing primordium stage, drives expression to a thin stripe in the posterior compartment that corresponds to the dorsal-ventral compartment boundary. The ME maintains the initial activated transcriptional state conferred by the C enhancer and contributes to the expansion, by growth, of its expression domain throughout the posterior compartment. Communication between the ME and the C enhancer also contributes to repression of gene expression in anterior cells. Most interestingly, we present evidence that enhancers and MEs of different genes are interchangeable modules whose communication is involved in restricting and expanding the domains of gene expression. Our results emphasize the modular role of MEs in regulation of gene expression within growing tissues.

A strand-specific switch in noncoding transcription switches the function of a Polycomb/Trithorax response element

“…1a) 20,25 . The latter site contains a PRE/TRE that has been characterized in several transgenic assays, and can maintain both silencing and activation of reporter gene activity in a PcG- and TrxG- dependent manner 22,23,26 .…”

“…We propose that the forward strand ncRNA promotes silencing by facilitating pairing between PRE/TREs. PRE/TRE pairing has been shown to be essential for maximum silencing by the vg PRE/TRE 26 , and this silencing is genetically dependent on the PcG 23,26 . Thus we propose that forward strand-induced pairing may facilitate or stabilize PcG mediated pairing-dependent silencing (Fig.…”

“…In this way, multiple self-reinforcing events could contribute to stable switching of the PRE/TRE into an active state. The vg PRE/TRE responds to TrxG mutations by loss of activation 23 . Whether TrxG-dependent activation acts via the ncRNAs will be a key question for future studies.…”

Genomic dimensions of Su(H)-targeted regulatory belts inDrosophila

“…The 8/29 known Notch-target enhancers neither overlap the 1344 SUH-RBs nor lie within 1 kb of them. These 8 pertain to the following enhancers: the broad (br) early enhancer (brE) (Fuchs et al 2012;Jia et al 2014), a gcm glial enhancer (Jones et al 2004), a hedgehog posterior wing margin enhancer (Pérez et al 2011), a salm wing enhancer (Guss et al 2001), a Ser wing enhancer (Yan et al 2004), the Sox15 sensory organ socket cell enhancer (Miller et al 2009), the sparkling (spa) cone cell enhancer of shaven (sv) (Fu et al 1998;Swanson et al 2010), and the vg quadrant enhancer (QE) (Guss et al 2001). However, many of these loci have other non-overlapping SUH-RBs elsewhere in the locus.…”

Drosophila DNA-Binding Proteins in Polycomb Repression

“…The activity of PREs can change under certain conditions: instead of repression, they can provide for activation of reporter genes [86][87][88][89][90]. This is mediated by Trithorax group (TrxG) activator proteins, which also bind to PREs and can antagonize PcG activity.…”