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. 2022 Feb 22;7(4):e150894. doi: 10.1172/jci.insight.150894

Figure 8. Zfp277 target genes in murine colon.

Figure 8

Posterior Hoxd genes are Zfp277 transcriptional targets. (A) Heatmap of differentially expressed genes in colon mucosa from 3 WT mice and 3 Zfp277–/– littermates. (B) Top 16 upregulated genes from RNA-Seq, excluding immunoglobulins. Genes in the Hoxd cluster are highlighted in red. (C) Schematic of the murine Hoxd posterior gene clusters. (D) qPCR of Hoxd13 mRNA expression in colon mucosal tissue from WT and Zfp277–/– mice. Values represent mean ± SEM (n = 3 each). (E) ZNF277 represses HOXD13 gene expression. HOXD13 immunoblot of proteins extracted from ZNF277 CRISPR cell- and control cell–derived xenograft tumors (2 separate tumors from each group). (F) Model illustrating the role of ZNF277/Zfp277 in intestinal tumorigenesis. ZNF277, normally expressed in TACs but not in differentiated enterocytes, maintains intestinal homeostasis. Aberrant WNT signaling stimulates ZNF277 overexpression in TACs. ZNF277 interacts with BMI1 in the PRC1 complex and represses p21WAF1 expression, thereby stimulating cell proliferation and attenuating cell senescence, as well as enhancing tumorigenesis and progressive neoplasia.