Structural insights into AT-rich DNA recognition by SALL family proteins

Ru, W.; Koga, T.; Wang, X.; Guo, Q.; Gearhart, M.; Zhao, S.; Murphy, M.; Kawakami, H.; Corcoran, D.; Zhang, J.; Zhu, Z.; Yao, X.; Kawakami, Y.; Xu, C.

doi:10.1101/2022.06.13.496009

bioRxiv · 10.1101/2022.06.13.496009

Structural insights into AT-rich DNA recognition by SALL family proteins

Ru, W.·Koga, T.·Wang, X.·Guo, Q.·Gearhart, M.·Zhao, S.·Murphy, M.·Kawakami, H.·Corcoran, D.·Zhang, J.·Zhu, Z.·Yao, X.·Kawakami, Y.·Xu, C.

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Abstract

Spalt-like 4 (SALL4) plays an essential role in controlling the pluripotent property of embryonic stem cells (ESCs) via binding to AT-rich regions of genomic DNA. Here we present crystal structures of the the zinc finger cluster 4 (ZFC4) domain of SALL4 (SALL4ZFC4) bound with different double stranded DNAs containing a conserved AT-rich motif. In the structures, two zinc fingers of SALL4ZFC4 coordinatively recognize an AATA tetranucleotide. We also solved the DNA-bound structures of SALL3ZFC4 and SALL4ZFC1. These structures illuminate a common recognition mode for AT-rich DNA by the SALL family proteins. The DNA binding activity is essential for SALL4 function as DNA-binding defective mutants of mouse Sall4 failed to repress aberrant gene expression in Sall4-/- mESCs. Thus, these analyses provide new insights into the mechanisms of action underlying SALL family in controlling cell fate via preferentially targeted to AT-rich sites within genomic DNAs during cell differentiation.

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Ru, W., Koga, T., Wang, X., Guo, Q., Gearhart, M., Zhao, S., Murphy, M., Kawakami, H., Corcoran, D., Zhang, J., Zhu, Z., Yao, X., Kawakami, Y., Xu, C.. 2022-06-14. Structural insights into AT-rich DNA recognition by SALL family proteins. https://doi.org/10.1101/2022.06.13.496009

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