Silencers in abdominal-B, a homeotic Drosophila gene.

Abstract

Homeotic genes determine the developmental fates of cells. Restriction of their expression along the body axis is of prime importance for normal development. We searched for cis‐regulatory sequences within Abdominal‐B (Abd‐B), a homeotic Drosophila gene, by testing genomic Abd‐B fragments for their ability to confer beta‐galactosidase (beta‐gal) expression in transformed embryos. One of the Abd‐B fragments, called IAB5, mediates a beta‐gal pattern restricted along the body axis to the Abd‐B expression domain. Alterations of the IAB5 pattern in gap mutants provide evidence that the protein products of the gap genes hunchback, Krüppel and knirps act as repressors through IAB5. The anterior Abd‐B expression limit is apparently determined by Krüppel repression, whereas the knirps repressor may be responsible for the graded Abd‐B expression within the Abd‐B domain. IAB5 and two other fragments called MCP and FAB show region‐specific silencing activity: they suppress at a distance beta‐gal expression mediated by a linked heterologous enhancer. Silencing requires hunchback as well as Polycomb function and evidently provides maintenance of Abd‐B expression limits throughout embryogenesis. We conclude that transcriptional repression is a key mechanism operating at multiple levels to control Abd‐B expression. The striking similarities between the control of Abd‐B and of Ultrabithorax, another homeotic Drosophila gene, may point to a universal principle underlying homeotic gene regulation.

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

“…We have evidence that, at the endogenous locus, the IAB5 enhancer in fact is recruited selectively only to the AbdB promoter by a tethering mechanism (R.A.D., unpublished data). In addition, all of the existing data indicate that the iab enhancers are active only later in development, when they begin to direct expression of the neighboring homeotic genes (4,16,17,36). However, we cannot discount the possibility that the intergenic transcription is directed by existing or as yet unknown enhancers in the BX-C.…”

“…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).…”

“…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.…”

Identification of Bmi1-interacting proteins as constituents of a multimeric mammalian polycomb complex.

“…Pc-G proteins bind to specific regulatory regions. so-called Pc-G response elements (PREs), which are necessary for maintaining the repressed state of homeotic genes (Miiller and Bienz 1991;Busturia and Bienz 1993;Simon et al 1993;Chan et al 1994;Chiang et al 1995). Little is known, however, about how Pc-G proteins interact molecularly or how they acquire PRE binding site specificity.…”

Evolving enhancer-promoter interactions within the tinman complex of the flour beetle,Tribolium castaneum

“…S11 in the supplementary material). The IAB5 enhancer (Busturia and Bienz, 1993) activates lacZ expression in the presumptive abdomen (Fig. 5A), but fails to activate white (Fig.…”