Tài liệu Báo cáo khoa học: Long-distance interactions between enhancers and promoters The case of

REVIEW ARTICLE

Long-distance interactions between enhancers and

promoters

The case of the Abd-B domain of the Drosophila bithorax complex

La´ szlo´ Sipos and Henrik Gyurkovics

Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary

Introduction

The normal development of eukaryotic organisms

requires a precise and coordinated control of gene

expression, both spatially and temporally. In the case

of genes with a highly complex expression pattern, this

is achieved through the action of a large set of enhanc￾ers, which are often located at a considerable distance

from the regulated gene. Accordingly, one of the key

questions involved in an understanding of complex

gene regulation is how distant enhancers communicate

with their target promoters. Despite its importance,

the available scientific data relating to this question are

still extremely scarce. In this respect, one of the best￾studied systems is the regulation of the homeotic

Abdominal-B (Abd-B) gene in Drosophila.

Abd-B, one of the three genes in the bithorax complex

(BX-C), determines the identity of the posterior-most

segments in the fly. One Abd-B transcript (class A tran￾script) is responsible for the proper identity of abdom￾inal segments 5–8, while three other transcripts are

required for the identity of abdominal segment 9 and

also that of abdominal segment 10 (for examples see

[1,2]). Here we focus on the transcriptional unit coding

for the class A transcript, and refer to it and its regula￾tory regions as the Abd-B domain. The expression pat￾tern of Abd-B is regulated by a set of large (over 10 kb),

autonomous cis-regulatory domains, iab-5, iab-6, iab-7

and iab-8 in segments A5, A6, A7 and A8, respectively

(reviewed in [3,4]). As illustrated in Fig. 1A, these

cis-regulatory domains are located downstream of the

Abd-B transcription unit, and, as is the case for the other

Keywords

Abd-B; chromatin structure; Drosophila;

homeotic genes; promoter targeting

Correspondence

H. Gyurkovics, Institute of Genetics,

Biological Research Center, Hungarian

Academy of Sciences, H-6726 Szeged,

Temesvari krt. 62, Hungary

Fax: +36 62 433503

Tel: +36 62 599687

E-mail: Henrik@brc.hu

(Received 21 February 2005, accepted

10 May 2005)

doi:10.1111/j.1742-4658.2005.04757.x

Abdominal-B (Abd-B) is a complex homeotic gene with a difficult task: one

transcript determines the identity of four different abdominal segments

throughout development in Drosophila. Although an increasing amount of

information is available about the structure and the functioning of the reg￾ulatory regions that determine the expression pattern of Abd-B, it is still

not clear how these regulatory regions can contact the distantly located

(several tens of kilobases away) promoter in the nucleus, what mechanism

restricts promiscuous enhancers to this specific interaction, and how differ￾ent regulatory regions replace one another at the same promoter in subse￾quent abdominal segments. Moreover, several of these regulatory regions

have to act over chromatin domain boundaries and extensive inactive chro￾matin domains, similarly to the situation found in the chicken beta-globin

cluster. In this minireview we survey mechanisms and factors that may be

involved in mediating specific interactions between the Abd-B promoter

and its regulatory regions.

Abbreviations

Abd-B, Abdominal-B gene; BX-C, bithorax complex; Pc-G, polycomb-group; PREs, polycomb response elements; PTS, promoter targeting

sequence; trx-G, trithorax-group; TREs, trithorax response elements; tmr, transvection-mediating region.

FEBS Journal 272 (2005) 3253–3259 ª 2005 FEBS 3253