Limits...
Identification of highly conserved putative developmental enhancers bound by SOX3 in neural progenitors using ChIP-Seq.

McAninch D, Thomas P - PLoS ONE (2014)

Bottom Line: SOX3 binding was identified at over 8,000 sites, most of which were intronic or intergeneic and were significantly associated with neurodevelopmental genes.In addition, we identified a subset of highly conserved putative enhancers for CNS development genes common to SOXB1 members in NP cells, all of which contained the SOX consensus motif (ACAAWR).Together these data implicate SOX3 in the direct regulation of hundreds of NP genes and provide molecular insight into the overlapping roles of SOXB1 proteins in CNS development.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, School of Molecular & Biomedical Science and Robinson Research Institute, The University of Adelaide, Adelaide, Australia.

ABSTRACT
The transcription factor SOX3 is expressed within most neural progenitor (NP) cells of the vertebrate central nervous system (CNS) and is essential for normal brain development in mice and humans. However, despite the widespread expression of Sox3, CNS defects in mice are relatively mild due to functional redundancy with the other SOXB1 sub-group members Sox1 and Sox2. To further understand the molecular function of SOX3, we investigated the genome-wide binding profile of endogenous SOX3 in NP cells using ChIP-seq. SOX3 binding was identified at over 8,000 sites, most of which were intronic or intergeneic and were significantly associated with neurodevelopmental genes. The majority of binding sites were moderately or highly conserved (phastCons scores >0.1 and 0.5, respectively) and included the previously characterised, SOXB1-binding Nestin NP cell enhancer. Comparison of SOX3 and published ChIP-Seq data for the co-activator P300 in embryonic brain identified hundreds of highly conserved putative enhancer elements. In addition, we identified a subset of highly conserved putative enhancers for CNS development genes common to SOXB1 members in NP cells, all of which contained the SOX consensus motif (ACAAWR). Together these data implicate SOX3 in the direct regulation of hundreds of NP genes and provide molecular insight into the overlapping roles of SOXB1 proteins in CNS development.

Show MeSH
SOX3 is implicated in an interchromosomal regulatory network.Graphical representation of potential long range intra- and interchromosomal interactions as identified by overlap of SOX3 peaks with RNAPII ChIA-PET peaks. Blue circles are sites present in both SOX3 and RNAPII datasets, while green circles are the linked genomic regions present only in the RNAPII dataset. The nearest TSS is labelled for the common binding sites.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4237438&req=5

pone-0113361-g005: SOX3 is implicated in an interchromosomal regulatory network.Graphical representation of potential long range intra- and interchromosomal interactions as identified by overlap of SOX3 peaks with RNAPII ChIA-PET peaks. Blue circles are sites present in both SOX3 and RNAPII datasets, while green circles are the linked genomic regions present only in the RNAPII dataset. The nearest TSS is labelled for the common binding sites.

Mentions: A recent study has published a dataset for chromatin interaction analysis with paired end tagging (ChIA-Pet) of RNA polymerase II in neural stem cells [17]. They identified more than 5,000 putative enhancers linked to the promoter of genes on different chromosomes (interchromosomal interactions), as well as more than 10,000 enhancers linked to distant genes on the same chromosome. We sought to identify whether SOX3 could be linked to any of these putative inter- or intra- chromosomal enhancers identified from a neural stem cell population. From the 8067 SOX3 peaks identified, 97 overlapped with potential long-range enhancers (a significant overlap, P<0.001, with an expected overlap of 34 by chance) that can be linked to 304 and 246 inter- and intrachromosomal promoters, respectively. For example, SOX3 binds an intronic enhancer within Tex14 (Figure 5) that can be linked to 263 different promoters and enhancers. This putative enhancer has a phastCons score of 0.12, moderate evolutionary conservation, and features a single SOX binding site. These data suggest that SOX3 may be involved in complex, long-range gene regulation.


Identification of highly conserved putative developmental enhancers bound by SOX3 in neural progenitors using ChIP-Seq.

McAninch D, Thomas P - PLoS ONE (2014)

SOX3 is implicated in an interchromosomal regulatory network.Graphical representation of potential long range intra- and interchromosomal interactions as identified by overlap of SOX3 peaks with RNAPII ChIA-PET peaks. Blue circles are sites present in both SOX3 and RNAPII datasets, while green circles are the linked genomic regions present only in the RNAPII dataset. The nearest TSS is labelled for the common binding sites.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4237438&req=5

pone-0113361-g005: SOX3 is implicated in an interchromosomal regulatory network.Graphical representation of potential long range intra- and interchromosomal interactions as identified by overlap of SOX3 peaks with RNAPII ChIA-PET peaks. Blue circles are sites present in both SOX3 and RNAPII datasets, while green circles are the linked genomic regions present only in the RNAPII dataset. The nearest TSS is labelled for the common binding sites.
Mentions: A recent study has published a dataset for chromatin interaction analysis with paired end tagging (ChIA-Pet) of RNA polymerase II in neural stem cells [17]. They identified more than 5,000 putative enhancers linked to the promoter of genes on different chromosomes (interchromosomal interactions), as well as more than 10,000 enhancers linked to distant genes on the same chromosome. We sought to identify whether SOX3 could be linked to any of these putative inter- or intra- chromosomal enhancers identified from a neural stem cell population. From the 8067 SOX3 peaks identified, 97 overlapped with potential long-range enhancers (a significant overlap, P<0.001, with an expected overlap of 34 by chance) that can be linked to 304 and 246 inter- and intrachromosomal promoters, respectively. For example, SOX3 binds an intronic enhancer within Tex14 (Figure 5) that can be linked to 263 different promoters and enhancers. This putative enhancer has a phastCons score of 0.12, moderate evolutionary conservation, and features a single SOX binding site. These data suggest that SOX3 may be involved in complex, long-range gene regulation.

Bottom Line: SOX3 binding was identified at over 8,000 sites, most of which were intronic or intergeneic and were significantly associated with neurodevelopmental genes.In addition, we identified a subset of highly conserved putative enhancers for CNS development genes common to SOXB1 members in NP cells, all of which contained the SOX consensus motif (ACAAWR).Together these data implicate SOX3 in the direct regulation of hundreds of NP genes and provide molecular insight into the overlapping roles of SOXB1 proteins in CNS development.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, School of Molecular & Biomedical Science and Robinson Research Institute, The University of Adelaide, Adelaide, Australia.

ABSTRACT
The transcription factor SOX3 is expressed within most neural progenitor (NP) cells of the vertebrate central nervous system (CNS) and is essential for normal brain development in mice and humans. However, despite the widespread expression of Sox3, CNS defects in mice are relatively mild due to functional redundancy with the other SOXB1 sub-group members Sox1 and Sox2. To further understand the molecular function of SOX3, we investigated the genome-wide binding profile of endogenous SOX3 in NP cells using ChIP-seq. SOX3 binding was identified at over 8,000 sites, most of which were intronic or intergeneic and were significantly associated with neurodevelopmental genes. The majority of binding sites were moderately or highly conserved (phastCons scores >0.1 and 0.5, respectively) and included the previously characterised, SOXB1-binding Nestin NP cell enhancer. Comparison of SOX3 and published ChIP-Seq data for the co-activator P300 in embryonic brain identified hundreds of highly conserved putative enhancer elements. In addition, we identified a subset of highly conserved putative enhancers for CNS development genes common to SOXB1 members in NP cells, all of which contained the SOX consensus motif (ACAAWR). Together these data implicate SOX3 in the direct regulation of hundreds of NP genes and provide molecular insight into the overlapping roles of SOXB1 proteins in CNS development.

Show MeSH