PMID- 28077616 OWN - NLM STAT- MEDLINE DCOM- 20170919 LR - 20181113 IS - 1939-4586 (Electronic) IS - 1059-1524 (Print) IS - 1059-1524 (Linking) VI - 28 IP - 5 DP - 2017 Mar 1 TI - Different modes of enhancer-specific regulation by Runt and Even-skipped during Drosophila segmentation. PG - 681-691 LID - 10.1091/mbc.E16-09-0630 [doi] AB - The initial metameric expression of the Drosophila sloppy paired 1 (slp1) gene is controlled by two distinct cis-regulatory DNA elements that interact in a nonadditive manner to integrate inputs from transcription factors encoded by the pair-rule segmentation genes. We performed chromatin immunoprecipitation on reporter genes containing these elements in different embryonic genotypes to investigate the mechanism of their regulation. The distal early stripe element (DESE) mediates both activation and repression by Runt. We find that the differential response of DESE to Runt is due to an inhibitory effect of Fushi tarazu (Ftz) on P-TEFb recruitment and the regulation of RNA polymerase II (Pol II) pausing. The proximal early stripe element (PESE) is also repressed by Runt, but in this case, Runt prevents PESE-dependent Pol II recruitment and preinitiation complex (PIC) assembly. PESE is also repressed by Even-skipped (Eve), but, of interest, this repression involves regulation of P-TEFb recruitment and promoter-proximal Pol II pausing. These results demonstrate that the mode of slp1 repression by Runt is enhancer specific, whereas the mode of repression of the slp1 PESE enhancer is transcription factor specific. We propose a model based on these differential regulatory interactions that accounts for the nonadditive interactions between the PESE and DESE enhancers during Drosophila segmentation. CI - (c) 2017 Hang and Gergen. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution-Noncommercial-Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). FAU - Hang, Saiyu AU - Hang S AD - Department of Biochemistry and Cell Biology and Center for Developmental Genetics and. AD - Graduate Program in Biochemistry and Structural Biology, Stony Brook University, Stony Brook, NY 11794. FAU - Gergen, J Peter AU - Gergen JP AD - Department of Biochemistry and Cell Biology and Center for Developmental Genetics and john.peter.gergen@stonybrook.edu. LA - eng GR - R01 GM094401/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20170111 PL - United States TA - Mol Biol Cell JT - Molecular biology of the cell JID - 9201390 RN - 0 (DNA-Binding Proteins) RN - 0 (Drosophila Proteins) RN - 0 (Fushi Tarazu Transcription Factors) RN - 0 (Homeodomain Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Transcription Factors) RN - 0 (eve protein, Drosophila) RN - 0 (ftz protein, Drosophila) RN - 0 (run protein, Drosophila) RN - 0 (slp1 protein, Drosophila) SB - IM MH - Animals MH - Body Patterning/genetics MH - DNA-Binding Proteins/genetics/*metabolism MH - Drosophila/embryology/genetics/metabolism MH - Drosophila Proteins/genetics/*metabolism MH - Embryo, Nonmammalian/metabolism MH - Female MH - Fushi Tarazu Transcription Factors/genetics/metabolism MH - Gene Expression Regulation, Developmental MH - Genes, Insect MH - Homeodomain Proteins/genetics/*metabolism MH - Male MH - Nuclear Proteins/genetics/*metabolism MH - Promoter Regions, Genetic MH - Regulatory Sequences, Nucleic Acid MH - Transcription Factors/genetics/*metabolism PMC - PMC5328626 EDAT- 2017/01/13 06:00 MHDA- 2017/09/20 06:00 PMCR- 2017/05/16 CRDT- 2017/01/13 06:00 PHST- 2016/09/02 00:00 [received] PHST- 2016/12/13 00:00 [revised] PHST- 2017/01/04 00:00 [accepted] PHST- 2017/01/13 06:00 [pubmed] PHST- 2017/09/20 06:00 [medline] PHST- 2017/01/13 06:00 [entrez] PHST- 2017/05/16 00:00 [pmc-release] AID - mbc.E16-09-0630 [pii] AID - E16-09-0630 [pii] AID - 10.1091/mbc.E16-09-0630 [doi] PST - ppublish SO - Mol Biol Cell. 2017 Mar 1;28(5):681-691. doi: 10.1091/mbc.E16-09-0630. Epub 2017 Jan 11.