RRC ID 36299
著者 Sadasivam DA, Huang DH.
タイトル Maintenance of Tissue Pluripotency by Epigenetic Factors Acting at Multiple Levels.
ジャーナル PLoS Genet
Abstract Pluripotent stem cells often adopt a unique developmental program while retaining certain flexibility. The molecular basis of such properties remains unclear. Using differentiation of pluripotent Drosophila imaginal tissues as assays, we examined the contribution of epigenetic factors in ectopic activation of Hox genes. We found that over-expression of Trithorax H3K4 methyltransferase can induce ectopic adult appendages by selectively activating the Hox genes Ultrabithorax and Sex comb reduced in wing and leg discs, respectively. This tissue-specific inducibility correlates with the presence of paused RNA polymerase II in the promoter-proximal region of these genes. Although the Antennapedia promoter is paused in eye-antenna discs, it cannot be induced by Trx without a reduction in histone variants or their chaperones, suggesting additional control by the nucleosomal architecture. Lineage tracing and pulse-chase experiments revealed that the active state of Hox genes is maintained substantially longer in mutants deficient for HIRA, a chaperone for the H3.3 variant. In addition, both HIRA and H3.3 appeared to act cooperatively with the Polycomb group of epigenetic repressors. These results support the involvement of H3.3-mediated nucleosome turnover in restoring the repressed state. We propose a regulatory framework integrating transcriptional pausing, histone modification, nucleosome architecture and turnover for cell lineage maintenance.
巻・号 12(2)
ページ e1005897
公開日 2016-2-1
DOI 10.1371/journal.pgen.1005897
PII PGENETICS-D-15-01948
PMID 26926299
PMC PMC4771708
MeSH Animals Animals, Genetically Modified Antennapedia Homeodomain Protein / genetics Antennapedia Homeodomain Protein / metabolism Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster / embryology Drosophila melanogaster / genetics* Drosophila melanogaster / growth & development Epigenesis, Genetic* Gene Expression Regulation, Developmental* Histone Chaperones / genetics Histone Chaperones / metabolism Histones / metabolism Homeodomain Proteins / genetics Homeodomain Proteins / metabolism Larva Polycomb Repressive Complex 1 / genetics Polycomb Repressive Complex 1 / metabolism Polycomb-Group Proteins / genetics Polycomb-Group Proteins / metabolism Transcription Factors / genetics Transcription Factors / metabolism
IF 5.175
引用数 5
WOS 分野 GENETICS & HEREDITY
リソース情報
ショウジョウバエ DGRC#203892