PMID- 20435028 OWN - NLM STAT- MEDLINE DCOM- 20100830 LR - 20211020 IS - 1095-564X (Electronic) IS - 0012-1606 (Print) IS - 0012-1606 (Linking) VI - 344 IP - 2 DP - 2010 Aug 15 TI - Non-additive interactions involving two distinct elements mediate sloppy-paired regulation by pair-rule transcription factors. PG - 1048-59 LID - 10.1016/j.ydbio.2010.04.026 [doi] AB - The relatively simple combinatorial rules responsible for establishing the initial metameric expression of sloppy-paired-1 (slp1) in the Drosophila blastoderm embryo make this system an attractive model for investigating the mechanism of regulation by pair-rule transcription factors. This investigation of slp1 cis-regulatory architecture identifies two distinct elements, a proximal early stripe element (PESE) and a distal early stripe element (DESE) located from -3.1kb to -2.5kb and from -8.1kb to -7.1kb upstream of the slp1 promoter, respectively, that mediate this early regulation. The proximal element expresses only even-numbered stripes and mediates repression by Even-skipped (Eve) as well as by the combination of Runt and Fushi-tarazu (Ftz). A 272 basepair sub-element of PESE retains an Eve-dependent repression, but is expressed throughout the even-numbered parasegments due to the loss of repression by Runt and Ftz. In contrast, the distal element expresses both odd and even-numbered stripes and also drives inappropriate expression in the anterior half of the odd-numbered parasegments due to an inability to respond to repression by Eve. Importantly, a composite reporter gene containing both early stripe elements recapitulates pair-rule gene-dependent regulation in a manner beyond what is expected from combining their individual patterns. These results indicate that interactions involving distinct cis-elements contribute to the proper integration of pair-rule regulatory information. A model fully accounting for these results proposes that metameric slp1 expression is achieved through the Runt-dependent regulation of interactions between these two pair-rule response elements and the slp1 promoter. CI - Copyright 2010 Elsevier Inc. All rights reserved. FAU - Prazak, Lisa AU - Prazak L AD - Department of Biochemistry and Cell Biology and the Center for Developmental Genetics, Stony Brook University, Stony Brook, NY 11794-5215, USA. FAU - Fujioka, Miki AU - Fujioka M FAU - Gergen, J Peter AU - Gergen JP LA - eng GR - R01 GM050231/GM/NIGMS NIH HHS/United States GR - R01 GM050231-12/GM/NIGMS NIH HHS/United States GR - R01GM050231/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20100506 PL - United States TA - Dev Biol JT - Developmental biology JID - 0372762 RN - 0 (Transcription Factors) SB - IM MH - Animals MH - Animals, Genetically Modified MH - Blastoderm/metabolism/physiology MH - Drosophila/*genetics/metabolism MH - Embryo, Nonmammalian MH - *Gene Expression Regulation MH - Regulatory Sequences, Nucleic Acid MH - *Transcription Factors/genetics/metabolism/physiology PMC - PMC2914134 MID - NIHMS207834 EDAT- 2010/05/04 06:00 MHDA- 2010/08/31 06:00 PMCR- 2011/08/15 CRDT- 2010/05/04 06:00 PHST- 2009/10/22 00:00 [received] PHST- 2010/04/08 00:00 [revised] PHST- 2010/04/23 00:00 [accepted] PHST- 2010/05/04 06:00 [entrez] PHST- 2010/05/04 06:00 [pubmed] PHST- 2010/08/31 06:00 [medline] PHST- 2011/08/15 00:00 [pmc-release] AID - S0012-1606(10)00271-X [pii] AID - 10.1016/j.ydbio.2010.04.026 [doi] PST - ppublish SO - Dev Biol. 2010 Aug 15;344(2):1048-59. doi: 10.1016/j.ydbio.2010.04.026. Epub 2010 May 6.