Recently visited
Please sign in to see a list of articles you recently visited.
Recently updated
 SOX9
Homo sapiens
 HIF1A
Homo sapiens
 Pax6
Mus musculus
 PAX6
Homo sapiens
 Snai2
Mus musculus
 PPARA
Homo sapiens
 Ppara
Mus musculus
 Thrb
Mus musculus
 SNAI2
Homo sapiens
 Tbr1
Mus musculus
Transcription Factor Encyclopedia  BETA
Comments (post)
Richard M. Gronostajski (rgron@buffalo.edu) on July 03, 2008 wrote:
 There is no good evidence that NFIs bind zinc or need it for activity 
Overview

NFI gene family: NFIA will be the root article for the Nuclear Factor I (pronounced Nuclear Factor One) gene family. The NFI gene family is a metazoan-specific family of site-specific DNA-binding transcription/replication factors, with single members in simple animals including Drosophila melanogaster and C. elegans (nfi-1), 4 members in all vertebrates (NFIA, NFIB, NFIC and NFIX in humans) but no members in plants, fungi or prokaryotes. NFI was discovered as a site-specific DNA-binding protein in human cell extracts required for the replication of Adenoviral DNA in vitro. It was nearly simultaneously discovered as a transcription factor and named TGGCA-binding protein for its consensus binding site. This DNA binding activity was later shown to be encoded by 4 highly homologous genes in humans that are part of the NFI gene family. The N-terminal DNA-binding domains of all NFI proteins are highly homologous and the proteins bind as homo- or heterodimers to the consensus sequence TTGGCN5GCCAA. The DNA-binding specificity of all NFI proteins appears very similar or identical from C. elegans to humans. In mice, all 4 family members are expressed in multiple tissues in a complex overlapping pattern. NFI proteins can either activate or repress transcription depending both on the promoter and cell type being studied. The same promoter can be activated or repressed in different cell types. The DNA-binding domain of NFI proteins appears unique, although there is very distant homology to the MH1 domain of SMAD proteins. Because products of the 4 genes have similar DNA-binding activities, in most cases where NFI binding sites have been identified in mammalian promoters it is unclear which NFI family member is functioning at the site in vivo. Many NFI proteins contain a C-terminal heptamer sequence homologous to the CTD repeat of RNA polymerase II. Its function is unclear. NFI genes are alternatively spliced leading to as many as 10 isoforms from each gene, all containing the same DNA-binding domain. The mouse and human NFI homologs are >98% identical so any information from one is likely applicable to the other. Unfortunately, some labs have taken to calling NFI NF1 or NF-1, which causes great confusion with the Neurofibromatosis type 1 gene in Pubmed searches. NFI (pronounced Nuclear Factor One) is the correct name for this family.

NFIA: Little is known about NFIA function in humans, although recently patients were identified by Lu et al. (see Figures) who had constitutive deletions of the region encompassing NFIA and had agenesis or reduced formation of the corpus callosum, severe mental retardation and ureter dysgenesis. These phenotypes are similar to those seen in Nfia-deficient mice. Much more is known about Nfia function in mice (see Nfia).

Figures
FIGURE 1 Figure 1. CNS and Urinary Tract Defects in Five Individuals with 1p31.3 Rearrangements
From Lu et al. PLOS Genetics, Vol. 3, Issue 5, e80. (A-J) Brain CT or MRI show a thin corpus callosum in DGAP104 (arrow in A), DGAP089 (arrow in C), and DGAP205-1 (arrow in G); and agenesis of the corpus callosum in DGAP174 (asterisk in E) and DGAP205-1s (asterisk in I). Chiari type I malformation, a downward displacement of the tip of the cerebellar tonsils below the foramen magnum, was found in DGAP104 (arrowhead in A), DGAP174 (arrowhead in E), and DGAP205-1s (arrowhead in I). Congenital ventriculomegaly is present in DGAP089 (D), DGAP174 (F), and DGAP205-1s (J), and hydrocephalus was found in DGAP104 (B) and DGAP205-1 (H). An occipital shunt (arrow in B) was placed in DGAP104 to relieve severe hydrocephalus. (K) DGAP104 MRI shows a tethered spinal cord, with the extremity of the conus medullaris (arrow) at the level of the L4 vertebral body. Arrowhead shows a fishhook deformity of the lower sacral and coccygeal vertebrae. (L) VCUG of DGAP104 depicts left vesicoureteral reflux with retrograde tracking of dye through the ureter into the renal pelvis (arrow) and a right diverticulum at the ureterovesical junction (arrowhead). (M) Spine MRI of DGAP205-1 shows a tethered spinal cord with conus lying at the L3/L4 level (arrow). (N) VCUG of DGAP205-1 shows left vesicoureteral reflux (arrow). (O) Spine MRI of DGAP205-1s depicts a tethered spinal cord with conus lying at L5 (arrow).
This figure was created by the authors of this article. The authors of this article have provided the assurance that this figure constitutes their original work.