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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 is coexpressed on a cellular level with other Sox proteins and Mitf in B16 melanoma cells. Immunocytochemistry was carried out on B16 melanoma cells using antibodies against the long Sox5 isoform (A, C, F and G), Sox6 (I and K), Sox13 (M and O) and Sox9 (Q and S) (in red). B16 melanoma cells were additionally counterstained with antibodies directed against Sox10 (B and C) and Mitf (E, G, J, K, N, O, R and S) (all in green). Panels (A, B, E, F, I, J, M, N, Q and R) show single color recordings, panels (C, G, K, O, S) merged pictures. Nuclei of B16 melanoma cells were counterstained with DAPI (D, H, L, P and T).
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Figure 7: Sox5 is coexpressed on a cellular level with other Sox proteins and Mitf in B16 melanoma cells. Immunocytochemistry was carried out on B16 melanoma cells using antibodies against the long Sox5 isoform (A, C, F and G), Sox6 (I and K), Sox13 (M and O) and Sox9 (Q and S) (in red). B16 melanoma cells were additionally counterstained with antibodies directed against Sox10 (B and C) and Mitf (E, G, J, K, N, O, R and S) (all in green). Panels (A, B, E, F, I, J, M, N, Q and R) show single color recordings, panels (C, G, K, O, S) merged pictures. Nuclei of B16 melanoma cells were counterstained with DAPI (D, H, L, P and T).

Mentions: To study the occurrence of Sox proteins in B16 cells on a cellular level, we also performed co-immunocytochemistry. The vast majority of analyzed B16 cells indeed expressed Sox5 (compare Figure 7A and E to Figure 7D and H) as well as Sox6 (compare Figure 7I to Figure 7L) and Sox9 (compare Figure 7Q to Figure 7T), but not Sox13 (compare Figure 7M to Figure 7O and P). Importantly, B16 cells were also quite homogenous regarding their expression of Sox10 (Figure 7B) and Mitf (Figure 7F, J, N and R). As a consequence, Sox5, Sox6 and Sox9 were all coexpressed in most B16 cells with Sox10 as well as Mitf (Figure 7C, G, K and S).


The transcription factor Sox5 modulates Sox10 function during melanocyte development.

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

Sox5 is coexpressed on a cellular level with other Sox proteins and Mitf in B16 melanoma cells. Immunocytochemistry was carried out on B16 melanoma cells using antibodies against the long Sox5 isoform (A, C, F and G), Sox6 (I and K), Sox13 (M and O) and Sox9 (Q and S) (in red). B16 melanoma cells were additionally counterstained with antibodies directed against Sox10 (B and C) and Mitf (E, G, J, K, N, O, R and S) (all in green). Panels (A, B, E, F, I, J, M, N, Q and R) show single color recordings, panels (C, G, K, O, S) merged pictures. Nuclei of B16 melanoma cells were counterstained with DAPI (D, H, L, P and T).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 7: Sox5 is coexpressed on a cellular level with other Sox proteins and Mitf in B16 melanoma cells. Immunocytochemistry was carried out on B16 melanoma cells using antibodies against the long Sox5 isoform (A, C, F and G), Sox6 (I and K), Sox13 (M and O) and Sox9 (Q and S) (in red). B16 melanoma cells were additionally counterstained with antibodies directed against Sox10 (B and C) and Mitf (E, G, J, K, N, O, R and S) (all in green). Panels (A, B, E, F, I, J, M, N, Q and R) show single color recordings, panels (C, G, K, O, S) merged pictures. Nuclei of B16 melanoma cells were counterstained with DAPI (D, H, L, P and T).
Mentions: To study the occurrence of Sox proteins in B16 cells on a cellular level, we also performed co-immunocytochemistry. The vast majority of analyzed B16 cells indeed expressed Sox5 (compare Figure 7A and E to Figure 7D and H) as well as Sox6 (compare Figure 7I to Figure 7L) and Sox9 (compare Figure 7Q to Figure 7T), but not Sox13 (compare Figure 7M to Figure 7O and P). Importantly, B16 cells were also quite homogenous regarding their expression of Sox10 (Figure 7B) and Mitf (Figure 7F, J, N and R). As a consequence, Sox5, Sox6 and Sox9 were all coexpressed in most B16 cells with Sox10 as well as Mitf (Figure 7C, G, K and S).

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