Variant PRC1 competes with retinoic acid-related signals to repress Meis2 in distal forelimb bud
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ABSTRACT:
PROVIDER: PRJNA415062 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Suppression of Meis genes in the distal limb bud is required for Proximal-Distal (PD) specification of the forelimb. Polycomb group (PcG) factors play a role in downregulation of retinoic acid (RA)-related signals in the distal forelimb bud, causing Meis repression. It is, however, not known if downregulation of RA-related signals and PcG-mediated proximal genes repression are functionally linked. Here, we reveal that PcG factors and RA-related signals antagonize each other to polarize Meis2 expression along the PD axis. With mathematical modeling and simulation, we propose that PcG factors are required to adjust the threshold for RA-related signaling to regulate Meis2 expression. Finally, we show that a variant Polycomb repressive complex 1 (PRC1), incorporating PCGF3 and PCGF5, represses Meis2 expression in the distal limb bud. Taken together, we reveal a previously unknown link between PcG proteins and downregulation of RA-related signals to mediate the phase transition of Meis2 transcriptional status during forelimb patterning.
2018-09-07 | GSE105206 | GEO
Project description:Polycomb group (PcG) proteins play a pivotal role in silencing developmental genes and help to maintain various stem and precursor cells and regulate their differentiation. PcG factors also regulate dynamic and complex regional specification, particularly in mammals, but this activity is mechanistically not well understood. In this study, we focused on proximal-distal (PD) patterning of the mouse forelimb bud to elucidate how PcG factors contribute to a regional specification process that depends on developmental signals. Depletion of the RING1 proteins RING1A (RING1) and RING1B (RNF2), which are essential components of Polycomb repressive complex 1 (PRC1), led to severe defects in forelimb formation along the PD axis. We show that preferential defects in early distal specification in Ring1A/B-deficient forelimb buds accompany failures in the repression of proximal signal circuitry bound by RING1B, including Meis1/2, and the activation of distal signal circuitry in the prospective distal region. Additional deletion of Meis2 induced partial restoration of the distal gene expression and limb formation seen in the Ring1A/B-deficient mice, suggesting a crucial role for RING1-dependent repression of Meis2 and likely also Meis1 for distal specification. We suggest that the RING1-MEIS1/2 axis is regulated by early PD signals and contributes to the initiation or maintenance of the distal signal circuitry. This SuperSeries is composed of the SubSeries listed below.
2015-12-28 | GSE70077 | GEO
Project description:Polycomb group (PcG) proteins play a pivotal role in silencing of development-related genes and contribute to maintain various stem and precursor cells and regulate their differentiation. However, it is not well understood how PcG factors regulate dynamic and complex morphogenetic processes particularly in mammals. In this study, we focused on proximal-distal (PD) patterning of forelimb bud to elucidate how PcG factors contribute to regulation of morphogenetic processes that depends on developmental signals. Depletion of RING1 proteins, which are common components of both canonical and variant Polycomb repressive complex-1 (PRC1), led to dramatic deficiencies in forelimb formation. By using Ring1-deficient forelimb buds, we revealed the early defects in distal specification, which is due to the functional coupling of RING1 and retinoic acid (RA) signaling. RING1 activity is shown to antagonize with RA signals at Meis2 and likely Meis1, which are superior suppressors of distal formation program, in the prospective distal region of outgrowing forelimb bud. This study exhibits a first example showing how PcG factors interplay with developmental signals to mediate compartmentalization of elongating anlagen by regulating the expression of developmental genes.
2015-12-28 | GSE70075 | GEO
Project description:Polycomb group (PcG) proteins play a pivotal role in silencing of development-related genes and contribute to maintain various stem and precursor cells and regulate their differentiation. However, it is not well understood how PcG factors regulate dynamic and complex morphogenetic processes particularly in mammals. In this study, we focused on proximal-distal (PD) patterning of forelimb bud to elucidate how PcG factors contribute to regulation of morphogenetic processes that depends on developmental signals. Depletion of RING1 proteins, which are common components of both canonical and variant Polycomb repressive complex-1 (PRC1), led to dramatic deficiencies in forelimb formation. By using Ring1-deficient forelimb buds, we revealed the early defects in distal specification, which is due to the functional coupling of RING1 and retinoic acid (RA) signaling. RING1 activity is shown to antagonize with RA signals at Meis2 and likely Meis1, which are superior suppressors of distal formation program, in the prospective distal region of outgrowing forelimb bud. This study exhibits a first example showing how PcG factors interplay with developmental signals to mediate compartmentalization of elongating anlagen by regulating the expression of developmental genes.
2015-12-28 | GSE70076 | GEO
Project description:Polycomb group (PcG) proteins play a pivotal role in silencing of development-related genes and contribute to maintain various stem and precursor cells and regulate their differentiation. However, it is not well understood how PcG factors regulate dynamic and complex morphogenetic processes particularly in mammals. In this study, we focused on proximal-distal (PD) patterning of forelimb bud to elucidate how PcG factors contribute to regulation of morphogenetic processes that depends on developmental signals. Depletion of RING1 proteins, which are common components of both canonical and variant Polycomb repressive complex-1 (PRC1), led to dramatic deficiencies in forelimb formation. By using Ring1-deficient forelimb buds, we revealed the early defects in distal specification, which is due to the functional coupling of RING1 and retinoic acid (RA) signaling. RING1 activity is shown to antagonize with RA signals at Meis2 and likely Meis1, which are superior suppressors of distal formation program, in the prospective distal region of outgrowing forelimb bud. This study exhibits a first example showing how PcG factors interplay with developmental signals to mediate compartmentalization of elongating anlagen by regulating the expression of developmental genes.
2015-12-28 | GSE70074 | GEO
Project description:Polycomb group (PcG) proteins play a pivotal role in epigenetically silencing development-related genes, restricting their expression to appropriate tissues. However, in some instances PcG target genes must also be dynamically regulated in response to developmental signals encountered during morphogenesis. Here we examine the role of PcG factors in early forelimb bud patterning, a process that relies on various morphogenetic signals. Depletion of Ring1 proteins, which are essential components of Polycomb repressive complex-1 (PRC1), led to dramatic deficiencies in forelimb formation and proximal-distal regionalization. Gene expression analysis identified Meis2 and Meis1 as critical PRC1 targets genes in early distal specification, with PcG proteins counteracting retinoic acid (RA) signaling to control their expression. Importantly, in this system, PcG factors appear to function by adjusting the threshold for RA signaling, revealing an unexpected role of polycomb proteins in dynamic gene regulation during development. [Affymetrix] Mouse E10.5 forelimb buds of Ring1A-KO, Ring1A/B-dKO and RA-treated wild type were used for RNA extraction and hybridization on Affymetrix microarrays. [Agilent] ChIP analysis of mouse E10.5 whole forelimb buds against anti-H3K27me3 antibody.
2015-05-27 | E-GEOD-57990 | biostudies-arrayexpress
Project description:Polycomb group (PcG) proteins play a pivotal role in epigenetically silencing development-related genes, restricting their expression to appropriate tissues. However, in some instances PcG target genes must also be dynamically regulated in response to developmental signals encountered during morphogenesis. Here we examine the role of PcG factors in early forelimb bud patterning, a process that relies on various morphogenetic signals. Depletion of Ring1 proteins, which are essential components of Polycomb repressive complex-1 (PRC1), led to dramatic deficiencies in forelimb formation and proximal-distal regionalization. Gene expression analysis identified Meis2 and Meis1 as critical PRC1 targets genes in early distal specification, with PcG proteins counteracting retinoic acid (RA) signaling to control their expression. Importantly, in this system, PcG factors appear to function by adjusting the threshold for RA signaling, revealing an unexpected role of polycomb proteins in dynamic gene regulation during development.
2015-05-27 | GSE57990 | GEO
Project description:Polycomb repressive complexes 1 and 2 (PRC1 and 2) repress lineage inappropriate genes during development to maintain proper cellular identities. To reveal the function of a variant PRC1 containing PCGF1 (PCGF1-PRC1), we prepared PCGF1 interacting proteins by immunoprecipitation and characterized them by LC-MS/MS.
2022-11-30 | PXD036330 | Pride
Project description:The bat offers an alternative paradigm to the standard mouse and chick model of limb development as it has extremely divergent forelimbs (long digits supporting a wing) and hindlimbs (short digits and claws) due the distinct requirements of both aerial and terrestrial locomotion. We used a cross-species microarray approach to identify differentially expressed (DE) genes between the bat (Minniopterus natalensis) forelimb and hindlimb autopods at Carollia developmental stages (CS) 16 and CS17, and between the bat (CS17) and mouse (E13.5) forelimb autopods. Several DE genes were identified, including two homeobox genes, Meis2, a proximal limb-patterning gene, and Hoxd11, a gene involved in digit elongation. Both genes are significantly over-expressed in the developing bat forelimb as compared to the hindlimb and equivalently staged mouse forelimbs.
2014-02-15 | GSE51042 | GEO
Project description:R-loops are three-stranded nucleic acid structures that form naturally during transcription, especially over unmethylated CpG-rich promoters. In mESC, such promoters of developmental regulator genes are occupied by the Polycomb-repressor complexes PRC1 and PRC2. Here we have explored the possibility that R-loops form over Polycomb-repressed genes and play a role in their transcriptional silencing. Using single gene and genome-wide analyses, we show that R-loops form at a specific subset of PRC-target genes and contribute to Polycomb occupancy on chromatin. Removal of R-loops leads to an up-regulation of nascent and processed transcripts and the appearance of the elongating form of RNA polymerase II. In contrast, removal of PRC2 does not influence R-loop formation, transcriptional repression and PRC1 recruitment. We finally show that R-loops and PRC1 can repress Polycomb-target genes in the absence of PRC2. Our results uncover an unanticipated synergy between R-loops and PRC1 in Polycomb repression mechanisms.
2019-03-19 | GSE118115 | GEO