Juxtaposed Polycomb complexes co-regulate vertebral identity.
Best known as epigenetic repressors of developmental Hox gene transcription, Polycomb complexes alter chromatin structure by means of post-translational modification of histone tails. Depending on the cellular context, Polycomb complexes of diverse composition and function exhibit cooperative interaction or hierarchical interdependency at target loci. The present study interrogated the genetic, biochemical and molecular interaction of BMI1 and EED, pivotal constituents of heterologous Polycomb complexes, in the regulation of vertebral identity during mouse development. Despite a significant overlap in dosage-sensitive homeotic phenotypes and co-repression of a similar set of Hox genes, genetic analysis implicated eed and Bmi1 in parallel pathways, which converge at the level of Hox gene regulation. Whereas EED and BMI1 formed separate biochemical entities with EzH2 and Ring1B, respectively, in mid-gestation embryos, YY1 engaged in both Polycomb complexes. Strikingly, methylated lysine 27 of histone H3 (H3-K27), a mediator of Polycomb complex recruitment to target genes, stably associated with the EED complex during the maintenance phase of Hox gene repression. Juxtaposed EED and BMI1 complexes, along with YY1 and methylated H3-K27, were detected in upstream regulatory regions of Hoxc8 and Hoxa5. The combined data suggest a model wherein epigenetic and genetic elements cooperatively recruit and retain juxtaposed Polycomb complexes in mammalian Hox gene clusters toward co-regulation of vertebral identity.
Kim
Se Young
SY
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Paylor
Suzanne W
SW
Magnuson
Terry
T
Schumacher
Armin
A
D000818:Animals; D002843:Chromatin / Q000378:metabolism; D004475:Ectoderm; D047108:Embryonic Development / Q000235:genetics; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D051379:Mice; D020297:Mice, Congenic; D008815:Mice, Inbred Strains; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050436:Regulatory Elements, Transcriptional; D012097:Repressor Proteins / Q000378:metabolism*; D019170:Somites; D013131:Spine / Q000196:embryology* / Q000378:metabolism
C489421:Bmi1 protein, mouse; D002843:Chromatin; C107275:Eed protein, mouse; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1