Sox12 Deletion in the Mouse Reveals Nonreciprocal Redundancy with the Related Sox4 and Sox11 Transcription Factors

Abstract

The transcription factors Sox4 and Sox11 are important regulators of diverse developmental processes including heart, lung, pancreas, spleen, and B-cell development. Here we have studied the role of the related Sox12 as the third protein of the SoxC group both in vivo and in vitro. Despite widespread Sox12 expression during embryonic development, Sox12-deficient mice developed surprisingly normally, so that they were born alive, showed no gross phenotypic abnormalities, and were fertile in both sexes. Comparison with the related Sox4 and Sox11 revealed extensive overlap in the embryonic expression pattern but more uniform expression levels for Sox12, without sites of particularly high expression. All three Sox proteins furthermore exhibited comparable DNA-binding characteristics and functioned as transcriptional activators. Sox12 was, however, a relatively weak transactivator in comparison to Sox11. We conclude that Sox4 and Sox11 function redundantly with Sox12 and can compensate its loss during mouse development. Because of differences in expression levels and transactivation rates, however, functional compensation is not reciprocal.

Amyloid precursor protein regulates neurogenesis by antagonizing miR-574-5p in the developing cerebral cortex

“…Our study may uncover the reason for the low transactivation activity observed for Sox12, which might be associated with miR-574-5p bindings. In addition, Sox12 KO mice do not show significant abnormality 29 , however, mice with double KO of Sox12 and Sox11 exhibit earlier and more widespread neurogenic defect in neural cells survival and progenitors proliferation 30,33 . These studies indicate that Sox12 and Sox11 may share a transcription regulatory pathway that mediates embryonic neural stem cells.…”

“…6). Sox12 is a transcription factor that shares a high degree of homology in the HMG domain and the C-terminal transactivation domain with other members like Sox4 and Sox11 in the SoxC group 29,30 . Sox11 has shown to be important in the transcriptional regulation of gene expression for neuronal differentiation 31 .…”

Transcription Factors SOX4 and SOX11 Function Redundantly to Regulate the Development of Mouse Retinal Ganglion Cells

“…In comparison to Sox4 and Sox11, although the expression pattern of Sox12 in certain developing tissues including lung, gut and pancreas is similar, the biochemical property of weak binding activity to promoter DNA makes Sox12 a less important factor in the regulation of development (13). And indeed, no phenotype of Sox12 knock-out mice was observed (14). In addition, our study shows that abolishment of both Sox4 and Sox11 by Six3-cre recombinase disrupts the formation of RGCs by 80% at E16.5 and leads to the complete loss of RGCs at later stages, suggesting Sox12 either does not participate or plays a limited role in regulating the development of RGCs.…”

“…Sox12 knock-out mice are via-ble and do not exhibit obvious abnormal phenotypes, but the deficiency of either Sox4 or Sox11 is lethal to mice (13)(14)(15). The broad expression of SoxC genes has been reported in neural progenitor cells and mesenchymal cells in variant tissues during development (13,14), and they have been found to regulate cell differentiation, proliferation and survival in multiple organ lineages (16 -22). Recent studies on Sox4 and Sox11 imply their roles in retinal cell differentiation (23).…”

Syntenin-mediated regulation of Sox4 proteasomal degradation modulates transcriptional output

“…It has been described that SoxC family members have overlapping expression patterns and molecular properties (Dy et al, 2008). Sox4 and Sox11 have both been implicated in cardiac and neuronal development, whereas Sox12 appears redundant (Bergsland et al, 2006;Hoser et al, 2008;Bhattaram et al, 2010;Potzner et al, 2010). As C-terminal domains of other Sox family members diverge from SoxC family members, protea-somal regulation of Sox proteins appears confined to the SoxC family.…”