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The transcription factor Sox5 modulates Sox10 function during melanocyte development.

Stolt CC, Lommes P, Hillgärtner S, Wegner M - Nucleic Acids Res. (2008)

Bottom Line: The transcription factor Sox5 has previously been shown in chicken to be expressed in early neural crest cells and neural crest-derived peripheral glia.This modulatory activity involved Sox5 binding and recruitment of CtBP2 and HDAC1 to the regulatory regions of melanocytic Sox10 target genes and direct inhibition of Sox10-dependent promoter activation.Both binding site competition and recruitment of corepressors thus help Sox5 to modulate the activity of Sox10 in the melanocyte lineage.

View Article: PubMed Central - PubMed

Affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen, Fahrstrasse 17, D-91054 Erlangen, Germany.

ABSTRACT
The transcription factor Sox5 has previously been shown in chicken to be expressed in early neural crest cells and neural crest-derived peripheral glia. Here, we show in mouse that Sox5 expression also continues after neural crest specification in the melanocyte lineage. Despite its continued expression, Sox5 has little impact on melanocyte development on its own as generation of melanoblasts and melanocytes is unaltered in Sox5-deficient mice. Loss of Sox5, however, partially rescued the strongly reduced melanoblast generation and marker gene expression in Sox10 heterozygous mice arguing that Sox5 functions in the melanocyte lineage by modulating Sox10 activity. This modulatory activity involved Sox5 binding and recruitment of CtBP2 and HDAC1 to the regulatory regions of melanocytic Sox10 target genes and direct inhibition of Sox10-dependent promoter activation. Both binding site competition and recruitment of corepressors thus help Sox5 to modulate the activity of Sox10 in the melanocyte lineage.

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Sox5 gene expression in the melanocyte lineage. Expression of Sox5 (A, C, E, G, I, K, M and O) (red) was compared to occurrence of Mitf (B, C, F, G, J, K, N and O) (green) on transverse sections from the forelimb region of wild-type mice at 10.5 dpc (A–D), 12.5 dpc (E–H), 16.5 dpc (I–L) and postnatal day 3 (P3) (M–P). To visualize the region in which double positive cells were found, nuclei were counterstained with DAPI (D, H, L and P).
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Figure 2: Sox5 gene expression in the melanocyte lineage. Expression of Sox5 (A, C, E, G, I, K, M and O) (red) was compared to occurrence of Mitf (B, C, F, G, J, K, N and O) (green) on transverse sections from the forelimb region of wild-type mice at 10.5 dpc (A–D), 12.5 dpc (E–H), 16.5 dpc (I–L) and postnatal day 3 (P3) (M–P). To visualize the region in which double positive cells were found, nuclei were counterstained with DAPI (D, H, L and P).

Mentions: Whereas most Mitf-positive cells contained Sox5 at 10.5, 11.5 and 12.5 dpc (Figures 1I–L and 2A–H), Sox5 was absent from most Mitf-expressing cells at 16.5 dpc and postnatal day 3 (Figure 2I–P). This argues that Sox5 is expressed during embryonic development in melanoblasts, but disappears from these cells with their differentiation to melanocytes.Figure 2.


The transcription factor Sox5 modulates Sox10 function during melanocyte development.

Stolt CC, Lommes P, Hillgärtner S, Wegner M - Nucleic Acids Res. (2008)

Sox5 gene expression in the melanocyte lineage. Expression of Sox5 (A, C, E, G, I, K, M and O) (red) was compared to occurrence of Mitf (B, C, F, G, J, K, N and O) (green) on transverse sections from the forelimb region of wild-type mice at 10.5 dpc (A–D), 12.5 dpc (E–H), 16.5 dpc (I–L) and postnatal day 3 (P3) (M–P). To visualize the region in which double positive cells were found, nuclei were counterstained with DAPI (D, H, L and P).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2553580&req=5

Figure 2: Sox5 gene expression in the melanocyte lineage. Expression of Sox5 (A, C, E, G, I, K, M and O) (red) was compared to occurrence of Mitf (B, C, F, G, J, K, N and O) (green) on transverse sections from the forelimb region of wild-type mice at 10.5 dpc (A–D), 12.5 dpc (E–H), 16.5 dpc (I–L) and postnatal day 3 (P3) (M–P). To visualize the region in which double positive cells were found, nuclei were counterstained with DAPI (D, H, L and P).
Mentions: Whereas most Mitf-positive cells contained Sox5 at 10.5, 11.5 and 12.5 dpc (Figures 1I–L and 2A–H), Sox5 was absent from most Mitf-expressing cells at 16.5 dpc and postnatal day 3 (Figure 2I–P). This argues that Sox5 is expressed during embryonic development in melanoblasts, but disappears from these cells with their differentiation to melanocytes.Figure 2.

Bottom Line: The transcription factor Sox5 has previously been shown in chicken to be expressed in early neural crest cells and neural crest-derived peripheral glia.This modulatory activity involved Sox5 binding and recruitment of CtBP2 and HDAC1 to the regulatory regions of melanocytic Sox10 target genes and direct inhibition of Sox10-dependent promoter activation.Both binding site competition and recruitment of corepressors thus help Sox5 to modulate the activity of Sox10 in the melanocyte lineage.

View Article: PubMed Central - PubMed

Affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen, Fahrstrasse 17, D-91054 Erlangen, Germany.

ABSTRACT
The transcription factor Sox5 has previously been shown in chicken to be expressed in early neural crest cells and neural crest-derived peripheral glia. Here, we show in mouse that Sox5 expression also continues after neural crest specification in the melanocyte lineage. Despite its continued expression, Sox5 has little impact on melanocyte development on its own as generation of melanoblasts and melanocytes is unaltered in Sox5-deficient mice. Loss of Sox5, however, partially rescued the strongly reduced melanoblast generation and marker gene expression in Sox10 heterozygous mice arguing that Sox5 functions in the melanocyte lineage by modulating Sox10 activity. This modulatory activity involved Sox5 binding and recruitment of CtBP2 and HDAC1 to the regulatory regions of melanocytic Sox10 target genes and direct inhibition of Sox10-dependent promoter activation. Both binding site competition and recruitment of corepressors thus help Sox5 to modulate the activity of Sox10 in the melanocyte lineage.

Show MeSH
Related in: MedlinePlus