Distinct functions are implicated for the XXXX , -5, and -6 transcription factors in the regulation of intestine epithelial cell differentiation.

@entity1 @entity844 @entity43289 @entity37760 @entity1630 @entity15774 @entity70731
Based on conserved expression patterns, three members of the GATA family of transcriptional regulatory proteins, @entity70731 , are thought to be involved in the regulation of cardiogenesis and gut development. Functions for these factors are known in the heart, but relatively little is understood regarding their possible roles in the regulation of gut-specific gene expression. In this study, we analyze the expression and function of @entity70731 using three separate but complementary vertebrate systems, and the results support a function for these proteins in regulating the terminal-differentiation program of intestinal epithelial cells. We show that xGATA-4, -5, and -6 can stimulate directly activity of the promoter for the intestinal @entity844 -binding protein (xIFABP) gene, which is a marker for differentiated enterocytes. This is the first direct demonstration of a target for GATA factors in the vertebrate intestinal epithelium. Transactivation by xGATA-4, -5, and -6 is mediated at least in part by a defined proximal @entity1630 promoter element. The expression patterns for cGATA-4, -5, and -6 are markedly distinct along the proximal-distal villus axis. Transcript levels for cGATA-4 increase along the axis toward the villus tip; likewise, cGATA-5 transcripts are largely restricted to the distal tip containing differentiated cells. In contrast, the pattern of cGATA-6 transcripts is complementary to cGATA-5, with highest levels detected in the region of proliferating progenitor cells. Undifferentiated and proliferating @entity1 HT-29 cells express @entity43289 but not @entity15774 or @entity37760 . Upon stimulation to differentiate, the transcript levels for @entity37760 increase, and this occurs prior to increased transcription of the terminal differentiation marker intestinal alkaline phosphatase. At the same time, @entity43289 steady-state transcript levels decline appreciably. All of the data are consistent with evolutionarily conserved but distinct roles for these factors in regulating the differentiation program of intestinal epithelium. Based on this data, we suggest that @entity43289 might function primarily within the proliferating progenitor population, while @entity15774 and @entity37760 function during differentiation to activate terminal-differentiation genes including @entity1630 .
