ZBP-89 function in colonic stem cells and during butyrateinduced senescence

Ramon Ocadiz-Ruiz, Amanda L. Photenhauer, Michael M. Hayes, Lin Ding, Eric R. Fearon, Juanita L. Merchant

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


ZBP-89 (Zfp148, ZNF148) is a Kruppel-type zinc-finger family transcription factor that binds to GC-rich DNA elements. Earlier studies in cell lines demonstrated that ZBP- 89 cooperates with Wnt β-catenin signaling by inducing β-catenin gene expression. Since β-catenin levels are normally highest at the crypt base, we examined whether ZBP-89 is required for stem cell maintenance. Lineage-tracing using a Zfp148CreERT2 transgenic line demonstrated expression in both intestine and colonic stem cells. Deleting the Zfp148 locus in the colon using the Cdx2NLSCreERT2 transgene, reduced the size and number of polyps formed in the Apc-deleted mice. Since colon polyps form in the presence of butyrate, a short chain fatty acid that suppresses cell growth, we examined the direct effect of butyrate on colon organoid survival. Butyrate induced senescence of colon organoids carrying the Apc deletion, only when Zfp148 was deleted. Using quantitative PCR and chromatin immunoprecipitation, we determined that butyrate treatment of colon cell lines suppressed ZNF148 gene expression, inducing CDKN2a (p16Ink4a) gene expression. Collectively, Zfp148 mRNA is expressed in CBCs, and is required for stem cell maintenance and colonic transformation. Butyrate induces colonic cell senescence in part through suppression of ZBP-89 gene expression and its subsequent occupancy of the CDKN2A promoter.

Original languageEnglish (US)
Pages (from-to)94330-94344
Number of pages15
Issue number55
StatePublished - Nov 1 2017
Externally publishedYes


  • Apc
  • CDKN2A
  • ChIP-Seq
  • Organoids
  • SA-bGal

ASJC Scopus subject areas

  • Oncology


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