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Major transcriptome re-organisation and abrupt changes in signalling, cell cycle and chromatin regulation at neural differentiation in vivo.

Olivera-Martinez I, Schurch N, Li RA, Song J, Halley PA, Das RM, Burt DW, Barton GJ, Storey KG - Development (2014)

Bottom Line: We show that these changes are conserved across species and provide biological evidence for reduced proteasome efficiency and a novel lengthening of S phase.We further demonstrate that transcription of one such gene, HDAC1, is dependent on FGF signalling, making a novel link between signals that control neural differentiation and transcription of a core regulator of chromatin organisation.Our work implicates new signalling pathways and dynamics, cellular processes and epigenetic modifiers in neural differentiation in vivo, identifying multiple new potential cellular and molecular mechanisms that direct differentiation.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.

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Downregulation of genes encoding chromatin modifiers and HDAC1 regulation by FGF signalling. (A) Transcripts for key chromatin-modifying genes SMARCA2, JARID2 and HDAC1 are downregulated as neural differentiation begins, whereas expression of EP300, which counters the activity of HDAC1, increases (arrowheads indicate the most recently formed somite; black dashed lines indicate the position of transverse sections beneath each embryo). (B) FGF-presenting beads transplanted into the stem zone maintain local ectopic HDAC1 transcription (white arrow). (C) Beads presenting the FGFR inhibitor PD173074 locally repress HDAC1 transcription in the stem zone (white arrow). Scale bars: 100 µm.
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DEV112623F6: Downregulation of genes encoding chromatin modifiers and HDAC1 regulation by FGF signalling. (A) Transcripts for key chromatin-modifying genes SMARCA2, JARID2 and HDAC1 are downregulated as neural differentiation begins, whereas expression of EP300, which counters the activity of HDAC1, increases (arrowheads indicate the most recently formed somite; black dashed lines indicate the position of transverse sections beneath each embryo). (B) FGF-presenting beads transplanted into the stem zone maintain local ectopic HDAC1 transcription (white arrow). (C) Beads presenting the FGFR inhibitor PD173074 locally repress HDAC1 transcription in the stem zone (white arrow). Scale bars: 100 µm.

Mentions: It is possible that elongating S phase in the CNT allows time for epigenetic events to take place that facilitate large-scale transcriptome re-organisation. Consistent with this, we find a sharp downregulation of transcripts for genes encoding major chromatin-modifying proteins, including the ATP-dependent chromatin remodelling gene SMARCA2/Brahma homologue/BAF190B (Goodwin, 1997), the polycomb repressor complex (PRC)-associated gene JARID2 (Landeira and Fisher, 2011) and the histone deacetylase HDAC1, which is complemented by upregulation of EP300, a key histone acetylase (identified in GO and/or KEGG analyses, and validated by cloning of these genes and mRNA expression analysis in the embryo (Fig. 6A).Fig. 6.


Major transcriptome re-organisation and abrupt changes in signalling, cell cycle and chromatin regulation at neural differentiation in vivo.

Olivera-Martinez I, Schurch N, Li RA, Song J, Halley PA, Das RM, Burt DW, Barton GJ, Storey KG - Development (2014)

Downregulation of genes encoding chromatin modifiers and HDAC1 regulation by FGF signalling. (A) Transcripts for key chromatin-modifying genes SMARCA2, JARID2 and HDAC1 are downregulated as neural differentiation begins, whereas expression of EP300, which counters the activity of HDAC1, increases (arrowheads indicate the most recently formed somite; black dashed lines indicate the position of transverse sections beneath each embryo). (B) FGF-presenting beads transplanted into the stem zone maintain local ectopic HDAC1 transcription (white arrow). (C) Beads presenting the FGFR inhibitor PD173074 locally repress HDAC1 transcription in the stem zone (white arrow). Scale bars: 100 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4197544&req=5

DEV112623F6: Downregulation of genes encoding chromatin modifiers and HDAC1 regulation by FGF signalling. (A) Transcripts for key chromatin-modifying genes SMARCA2, JARID2 and HDAC1 are downregulated as neural differentiation begins, whereas expression of EP300, which counters the activity of HDAC1, increases (arrowheads indicate the most recently formed somite; black dashed lines indicate the position of transverse sections beneath each embryo). (B) FGF-presenting beads transplanted into the stem zone maintain local ectopic HDAC1 transcription (white arrow). (C) Beads presenting the FGFR inhibitor PD173074 locally repress HDAC1 transcription in the stem zone (white arrow). Scale bars: 100 µm.
Mentions: It is possible that elongating S phase in the CNT allows time for epigenetic events to take place that facilitate large-scale transcriptome re-organisation. Consistent with this, we find a sharp downregulation of transcripts for genes encoding major chromatin-modifying proteins, including the ATP-dependent chromatin remodelling gene SMARCA2/Brahma homologue/BAF190B (Goodwin, 1997), the polycomb repressor complex (PRC)-associated gene JARID2 (Landeira and Fisher, 2011) and the histone deacetylase HDAC1, which is complemented by upregulation of EP300, a key histone acetylase (identified in GO and/or KEGG analyses, and validated by cloning of these genes and mRNA expression analysis in the embryo (Fig. 6A).Fig. 6.

Bottom Line: We show that these changes are conserved across species and provide biological evidence for reduced proteasome efficiency and a novel lengthening of S phase.We further demonstrate that transcription of one such gene, HDAC1, is dependent on FGF signalling, making a novel link between signals that control neural differentiation and transcription of a core regulator of chromatin organisation.Our work implicates new signalling pathways and dynamics, cellular processes and epigenetic modifiers in neural differentiation in vivo, identifying multiple new potential cellular and molecular mechanisms that direct differentiation.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.

Show MeSH
Related in: MedlinePlus