Nutrition Guide

Mutations in Cbfa1/Runx2 are associated with the disease Cleidocranial dysostosis.

Cbfa1/Runx2 is key transcription factor associated with osteoblast differentiation.

This protein is a member of the RUNX family of transcription factors and has a Runt DNA-binding domain. It is essential for osteoblastic differentiation and skeletal morphogenesis and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex. Transcript variants of the gene that encode different protein isoforms result from the use of alternate promoters as well as alternate splicing.[

Checkpoint suppressor 1, also known as CHES1, is a human gene.[1]

This gene is a member of the forkhead/winged helix transcription factor family. Checkpoints are eukaryotic DNA damage-inducible cell cycle arrests at G1 and G2. Checkpoint suppressor 1 suppresses multiple yeast checkpoint mutations including mec1, rad9, rad53 and dun1 by activating a MEC1-independent checkpoint pathway. Alternative splicing is observed at the locus, resulting in distinct isoforms.[1]

POU domain, class 2, transcription factor 1, also known as POU2F1, is a human gene.[1]

Jumonji, AT rich interactive domain 1B, also known as JARID1B, is a human gene.[1]

NPAS3 or Neuronal PAS domain protein 3 is a brain-enriched transcription factor belonging to the bHLH-PAS superfamily of transcription factors, the members of which carry out diverse functions, including circadian oscillations, neurogenesis, toxin metabolism, hypoxia, and tracheal development. NPAS3 contains basic-helix-loop-helix structural motif and PAS domain, like the other proteins in the superfamily. Disruption of NPAS3 was found in one family affected by schizophrenia[1] and NPAS3 gene is thought to be associated with psychiatric illness and learning disability.[2][3] In a genetic study of several hundred subjects conducted in 2008, interacting haplotypes at the NPAS3 locus were found to affect the risk of schizophrenia and bipolar disorder.[4]

NPAS1 and NPAS3-deficient mice display behavioral abnormalities typical to the animal models of schizophrenia.[5]

According to the same study, NPAS1 and NPAS3 disruption leads to reduced expression of reelin, which is also consistently found to be reduced in the brains of human patients with schizophrenia and psychotic bipolar disorder. Among the 49 genomic regions that undergone rapid changes in humans compared with their evolutionary ancestors, NPAS3 was found to be located in the region 21.[6]

In a pharmacogenetical study, polymorphisms in NPAS3 gene were highly associated with response to iloperidone, a proposed atypical antipsychotic.[7]

bHLH transcription factors have been shown to have a wide array of functions in developmental processes.[3] More precisely, they have critical roles in the control of cellular differentiation, proliferation and regulation of oncogenesis.[3][4][5] To date, 242 eukaryotic proteins belonging to the HLH superfamily have been reported. They have varied expression patterns in all eukaryotes from yeast to humans.[6]

Structurally, bHLH proteins are characterised by a “highly conserved domain containing a stretch of basic amino acids adjacent to two amphipathic ?-helices separated by a loop”.[7][8]

These helices have important functional properties, forming part of the DNA binding and transcription activating domains. With respect to scleraxis, the bHLH region spans amino acid residues 78 to 131. A proline rich region is also predicted to lie between residues 161-170. A stretch of basic residues, which aids in DNA binding, is found closer to the N terminal end of scleraxis.[9][1]

HLH proteins that lack this basic domain have been shown to negatively regulate the activities of bHLH proteins and are called inhibitors of differentiation (Id).[10] Basic HLH proteins function normally as dimers and bind to a specific hexanucleotide DNA sequence (CAANTG) known as an E-box thus switching on the expression of various genes involved in cellular development and survival.

It is thought that early scleraxis expressing progenitor cells lead to the eventual formation of tendon tissue and other muscle attachments.[1] Scleraxis is involved in mesoderm formation and is expressed in the syndetomal (embryonic tissues that develop into tendon and blood vessels) compartment of developing somites (primitive segments or compartments of embryos).[2]

The scleraxis protein is a member of the basic-helix-loop-helix (bHLH) superfamily of transcription factors.[1] Currently two genes (SCXA and SCXB respectively) have been identified to code for identical scleraxis proteins.

By targeting the ZFP towards a specific DNA sequence and attaching the necessary effector domain, it is possible to downregulate or upregulate the expression of the gene(s) in question while using the same DNA-binding domain. The expression of a gene can also be downregulated by blocking elongation by RNA polymerase (without the need for an effector domain) in the coding region or alternatively, RNA itself can also be targeted.[2][1] Besides the obvious development of tools for the research of gene function, engineered ZFP-TFs have enormous therapeutic potential including correction of abnormal gene expression profiles (e.g. erbB-2 overexpression in human adenocarcinomas[3][4] and anti-retrovirals (e.g. HIV-1[5]).