Onecut Transcription Factors
Hepatocyte Nuclear Factor 6
Temporal regulation of enhancer function in intestinal epithelium: a role for Onecut factors. (1/6)
An intestine-specific gene regulatory region was previously identified near the second exon of the human adenosine deaminase (ADA) gene. In mammalian intestine, ADA is expressed at high levels only along the villi of the duodenal epithelium, principally if not exclusively in enterocytes. Within the ADA intestinal regulatory region, a potent duodenum-specific enhancer was identified that controls this pattern of expression. This enhancer has been shown to rely on PDX-1, GATA factors, and Cdx factors for its function. Upstream of the enhancer, a separate temporal regulatory region was identified that has no independent enhancer capability but controls the timing of enhancer activation. DNase I footprinting and electrophoretic mobility shift assays were used to begin to characterize temporal region function at the molecular level. In this manner, binding sites for the Onecut (OC) family of factors, YY1, and NFI family members were identified. Identification of the OC site was especially interesting, because almost nothing is known about the function of OC factors in intestine. In transgenic mice, mutation of the OC site to ablate binding resulted in a delay of 2-3 weeks in enhancer activation in the developing postnatal intestine, a result very similar to that observed previously when the entire temporal region was deleted. In mammals, the OC family is comprised of OC-1/HNF-6, OC-2, and OC-3. An examination of intestinal expression patterns showed that all three OC factors are expressed at detectable levels in adult mouse duodenum, with OC-2 predominant. In postnatal day 2 mice only OC-2 and OC-3 were detected in intestine, with OC-2 again predominant. (+info)Role of the Onecut transcription factors in pancreas morphogenesis and in pancreatic and enteric endocrine differentiation. (2/6)
The Onecut (OC) transcription factor HNF-6 (OC-1) is required during embryogenesis for pancreatic specification, morphogenesis and endocrine differentiation. In mammals, HNF-6 has two paralogs, OC-2 and OC-3, which share DNA-binding and transcriptional activation properties and have expression patterns that overlap with that of HNF-6. This suggested that OC-2 and OC-3 play redundant roles with HNF-6 in pancreas development. Here, we have addressed this hypothesis by analyzing the phenotype of mice knockout for the Onecut factors. We found that neither OC-2 nor OC-3 is required for pancreas specification. However, OC-2 plays partially redundant roles with HNF-6 in pancreas morphogenesis and in the differentiation of endocrine precursors. As similar molecular events drive endocrine differentiation in the pancreas and gastrointestinal tract, we also investigated if Onecut factors are involved in enteroendocrine differentiation. OC-2 and OC-3 were found to delineate specific antero-posterior regions of the gut around embryonic day 12.5. Later on, OC2 was expressed in several gut cell types, whereas OC-3 behaved as a specific marker of the enteroendocrine lineage. However, OC-2 and OC-3, alone or in combination, were dispensable for gut development and enteroendocrine differentiation. In conclusion, our data reveal partially redundant roles for HNF-6 and OC-2 in developing pancreas and identify new markers for antero-posterior patterning of the gut and for enteroendocrine differentiation. (+info)A ONECUT homeodomain protein communicates X chromosome dose to specify Caenorhabditis elegans sexual fate by repressing a sex switch gene. (3/6)
Sex is determined in Caenorhabditis elegans through a dose-dependent signal that communicates the number of X chromosomes relative to the ploidy, the number of sets of autosomes. The sex switch gene xol-1 is the direct molecular target of this X:A signal and integrates both X and autosomal components to determine sexual fate. X chromosome number is relayed by X signal elements (XSEs) that act cumulatively to repress xol-1 in XX animals, thereby inducing hermaphrodite fate. Ploidy is relayed by autosomal signal elements (ASEs), which counteract the single dose of XSEs in XO animals to activate xol-1 and induce the male fate. Our goal was to identify and characterize new XSEs and further analyze known XSEs to understand the principles by which a small difference in the concentration of an intracellular signal is amplified to induce dramatically different developmental fates. We identified a new XSE, the ONECUT homeodomain protein CEH-39, and showed that it acts as a dose-dependent repressor of xol-1 transcript levels. Unexpectedly, most other XSEs also repress xol-1 predominantly, but not exclusively, at the transcript level. The twofold difference in X dose between XO and XX animals is translated into the male vs. hermaphrodite fate by the synergistic action of multiple, independent XSEs that render xol-1 active or inactive, primarily through transcriptional regulation. (+info)Onecut is a direct neural-specific transcriptional activator of Rx in Ciona intestinalis. (4/6)
(+info)Onecut transcription factors act upstream of Isl1 to regulate spinal motoneuron diversification. (5/6)
(+info)MicroRNA-9 promotes the switch from early-born to late-born motor neuron populations by regulating Onecut transcription factor expression. (6/6)
(+info)Onecut transcription factors are a family of proteins that regulate gene expression by binding to specific DNA sequences in the promoter or enhancer regions of target genes. They are named after the Onecut homeobox gene, which was originally identified in mice and is also known as HNF6 (hepatocyte nuclear factor 6).
Onecut transcription factors contain a conserved domain called the Onecut/HNF6 domain, which is responsible for DNA binding. They play important roles in various biological processes, including cell fate determination, organ development, and metabolism. In particular, they have been shown to be crucial for the development of the pancreas, liver, and nervous system.
Mutations in Onecut transcription factors have been associated with several human diseases, including diabetes, pancreatic cancer, and neurological disorders. Therefore, understanding the function and regulation of these proteins is important for developing new therapies for these conditions.
Hepatocyte Nuclear Factor 6 (HNF-6) is a transcription factor that belongs to the forkhead box (FOX) protein family and is primarily expressed in the liver, pancreas, and intestine. It plays crucial roles in regulating gene expression during embryonic development and maintaining tissue-specific functions in adults.
In the liver, HNF-6 helps control the differentiation and maturation of hepatocytes (the primary functional cells of the liver) by regulating genes involved in various metabolic processes such as glucose, lipid, and drug metabolism. Additionally, HNF-6 has been implicated in the development and function of bile ducts and pancreatic exocrine cells.
Mutations in the gene encoding HNF-6 (FOXA2) have been associated with several human diseases, including monogenic diabetes and congenital diarrhea disorders.
Transcription factors are proteins that play a crucial role in regulating gene expression by controlling the transcription of DNA to messenger RNA (mRNA). They function by binding to specific DNA sequences, known as response elements, located in the promoter region or enhancer regions of target genes. This binding can either activate or repress the initiation of transcription, depending on the properties and interactions of the particular transcription factor. Transcription factors often act as part of a complex network of regulatory proteins that determine the precise spatiotemporal patterns of gene expression during development, differentiation, and homeostasis in an organism.