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.
Chopra
Vivek S
VS
Division of Genetics, Center for Integrative Genomics, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
Hong
Joung-Woo
JW
Levine
Michael
M
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