Regulation of Hox gene activity by transcriptional elongation in Drosophila.
Hox genes control the anterior-posterior patterning of most metazoan embryos. Their sequential expression is initially established by the segmentation gene cascade in the early Drosophila embryo [1]. The maintenance of these patterns depends on the Polycomb group (PcG) and trithorax group (trxG) complexes during the remainder of the life cycle [2]. We provide both genetic and molecular evidence that the Hox genes are subject to an additional tier of regulation, i.e., at the level of transcription elongation. Both Ultrabithorax (Ubx) and Abdominal-B (Abd-B) genes contain stalled or paused RNA polymerase II (Pol II) even when silent [3, 4]. The Pol II elongation factors Elongin-A and Cdk9 are essential for optimal Ubx and Abd-B expression. Mitotic recombination assays suggest that these elongation factors are also important for the regulation of Notch-, EGF-, and Dpp-signaling genes. Stalled Pol II persists in tissues where Ubx and Abd-B are silenced by the PcG complex. We propose that stalling fosters both the rapid induction and precise silencing of Hox gene expression during development.
Division of Genetics, Center for Integrative Genomics, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
Vivek S
VS
Chopra
Joung-Woo
JW
Hong
Michael
M
Levine
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism; D014921:Wings, Animal / Q000033:anatomy & histology / Q000196:embryology
C062393:Abd-B proteins, Drosophila; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; C066177:Ubx protein, Drosophila; D042863:Cyclin-Dependent Kinase 9