MOTIVATION Recognition models for protein-DNA interactions, which allow the prediction of specificity for a DNA-binding domain based only on its sequence or the alteration of specificity through rational design, have long been a goal of computational biology. There has been some progress in constructing useful models, especially for C(2)H(2) zinc finger proteins, but it remains a challenging pr...

Thyroid transcription factor-1 (TITF-1) is a homeodomain containing transcription factor that binds to and selectively activates the expression of genes in thyroid and pulmonary epithelial cells. TITF-1 plays a critical role in gene expression and in organogenesis of lung and thyroid. In the present work, epitope-tagged TITF-1 proteins were used to identify the regions of the TITF-1 polypeptide...

Although the precise three-dimensional structure of a protein is an essential determinant of its function, it is sometimes desirable that parts of its structure not be too rigid. For example, when induced fit occurs in an antibody-antigen, receptorligand, or enzyme-substrate interaction, the protein and/or its partner must undergo a conformational change; structural flexibility can help minimiz...

The autosomal dominant disorders iris hypolasia (IH), iridogoniodysgenesis syndrome (IGDS) and Axenfeld-Rieger syndrome (ARS) are characterized by maldevelopment of the anterior segment of the eye associated with an increased risk of early-onset glaucoma. IH, IGDS and ARS are allelic disorders, as all three can result from mutations of the transcription factor PITX2. IH is the mildest of the th...

BACKGROUND Organizing signals such as Sonic hedgehog are thought to specify neuronal subtype identity by regulating the expression of homeodomain proteins in progenitors of the embryonic neural tube. One of these, Nkx2.2, is necessary and sufficient for the development of V3 interneurons. RESULTS We report that Olig genes, encoding basic helix-loop-helix (bHLH) proteins, are expressed in a su...

The cooperative binding of gene regulatory proteins to DNA is a common feature of transcriptional control in both prokaryotes and eukaryotes. It is generally viewed as a simple energy coupling, through protein-protein interactions, of two or more DNA-binding proteins. In this paper, we show that the simple view does not account for the cooperative DNA binding of a1 and alpha2, two homeodomain p...

A number of genes, spanning the evolutionary scale from yeast to mammals, that are involved in spatial and temporal patterning during development contain zinc finger and homeodomain motifs. One such zinc finger/homeodomain protein is Drosophila Zfh-1, a member of the zfh family of Drosophila genes, which is expressed in muscle precursors and is critical for the proper development of muscle. Her...

Atrial fibrillation (AF) is the most common cardiac arrhythmia in human population, with an estimated incidence of 1–2% young adults but increasing to more than 10% 80+ years patients. Pituitary Homeobox 2, Paired Like Homeodomain 2 (PITX2c) loss-of-function mice revealed that this homeodomain (HD)-containing transcription factor plays a pivotal role atrial electrophysiology and calcium homeost...

Interactions with cofactors regulate transcriptional activity and also help HOX proteins to achieve the specificity required for transcriptional regulation of target genes. In this study, we describe a novel protein/protein interaction of HOXB7 with poly (ADP-ribose) polymerase-1 (PARP-1) that involves the homeodomain of HOXB7 and the first zinc finger domain of PARP-1. Upon binding to PARP-1, ...