Chromatin domain boundaries in the Bithorax complex

Abstract

Eukaryotic chromosomes are thought to be organized into a series of discrete higher-order chromatin domains. This organization is believed to be important not only in the compaction of the chromatin fibre, but also in the utilization of genetic information. Critical to this model are the domain boundaries that delimit and segregate the chromosomes into units of independent gene activity. In Drosophila, such domain boundaries have been identified through two different approaches. On the one hand, elements like scs/scs' and the reiterated binding site for the SU(HW) protein have been characterized through their activity of impeding enhancer-promoter interactions when intercalated between them. Their role of chromatin insulators can protect transgenes from genomic position effects, thereby establishing independent functional domains within the chromosome. On the other hand, domain boundaries of the Bithorax complex (BX-C) like Fab-7 and Mcp have been identified through mutational analysis. Mcp and Fab-7, however, may represent a specific class of boundary elements; instead of separating adjacent domains that contain separate structural genes. Mcp and Fab-7 delimit adjacent cis-regulatory domains, each of which interacts independently with their target promoters. In this article, we review the genetic and molecular characteristics of the domain boundaries of the BX-C. We describe how Fab-7 functions to confine activating as well as repressive signals to the flanking regulatory domains. Although the mechanisms by which Fab-7 works as a domain boundary remain an open issue, we provide preliminary evidence that Fab-7 is not a mere insulator like scs or the reiterated binding site for the SU(HW) protein.

Transcription defines the embryonic domains of cis-regulatory activity at the Drosophila bithorax complex

“…If the initial activation of the cis-regulatory elements in the iab regions is dependent on the intergenic transcripts, then it would be necessary not only to have unique transcription patterns within each region but also to ensure that transcription does not spread from one region to the next. Our study provides evidence that the insulators that organize the different iab regions into discrete chromatin domains (8,14,15) act to regulate the intergenic transcription program in this way.…”

“…Genetic, transgenic, and molecular studies have identified a number of classes of distinct cis-regulatory elements within the iab regions capable of directing abdA and AbdB expression. Insulator DNAs have been identified at the boundaries of the iab8-iab7 domains (Frontabdominal-8, Fab8) (4), iab7-iab6 domains (Fab7) (5)(6)(7)(8)(9)(10), and iab5-iab4 domains (Miscadastral pigmentation, Mcp) ( Fig. 1 A) (7,11).…”

“…Although not all insulators are thought to act in the same way (12,13), it has been suggested that the BX-C insulators organize the different iab regions into discrete chromatin domains ( Fig. 1 A) (8,14,15). In this way, cis-regulatory elements within the separate domains are able to direct expression of abdA and AbdB in specific abdominal segments of the Drosophila embryo.…”

“…Indeed, transgenic studies have identified enhancers from the iab8 (IAB8) (4), iab7 (IAB7) (4), and iab5 (IAB5) (16,17) regions that drive expression in specific abdominal segments. Furthermore, elements capable of silencing gene transcription, Polycomb response elements, have been discovered in the iab8 (4), iab7 (10,18), and iab5 regions (17,19). It is likely that analogous cis-regulatory elements, capable of directing segment-specific gene expression, are present in the other iab regions but remain to be characterized.…”

GATA simple sequence repeats function as enhancer blocker boundaries

“…Boundary elements are known to function across species 16,18,19 and Drosophila melanogaster is used as a model system of choice to study such elements from different species taking genetic and cell biology approaches in the transgenic context [20][21][22] . Before going for transgenic experiments, we checked whether GATA repeats bind to specific proteins in the Drosophila embryo nuclear extract.…”