Adenoviral VEGF-A gene transfer induces angiogenesis and promotes bone formation in healing osseous tissues.

Background: Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. VEGF has been safely and efficiently applied to stimulate neovascularization in ischemic tissues in atherosclerotic patients. VEGF has an important role in bone repair by promoting angiogenesis and by stimulating major skeletal cell populations, chondrocytes, osteoblasts and osteoclasts.

Nucleotide and calcium-induced conformational changes in histone H1.

The principal constituents of chromatin, histone H1 (H1) and the nucleosome have essential roles in regulation of eukaryotic gene expression. However, mechanisms for the H1-dependent inactivation and for the ATP-dependent chromatin remodeling upon activation are largely unelucidated. Using circular dichroism (CD) analysis we show that ATP and other nucleotides and Ca2+ induce structural changes in H1.

The ATP/ADP binding domains of actin are conserved in nucleosome complexed with histone H1 and high mobility group-17 protein.

Chromatin has been proposed to share a common evolutionary origin and analogous mechanisms of action with various structures of cytoskeleton such as actin filaments. ATP has been shown to facilitate chromatin remodelling, but the exact site of its interaction with chromatin has not been elucidated. The facts, that ATP binds specifically to actin and promotes its polymerization, led us to characterize the possible domains involved in ATP binding in nucleosome.

Nucleotide recognition by histone H1 involves specific protein structures.

We have reported previously that histone H1 is capable of binding nucleotides such as ATP, GTP, ADP, and GDP in a specific manner. It is demonstrated here using labeling with the uv-crosslinkable ATP analog 8-azido-[alpha-32P]ATP that this ability is a unique characteristic of H1 among the histone proteins. Phosphate analogs such as AlF-4 efficiently counteract the labeling of H1, while they do not compete for labeling of histones H2A, H2B, H3, and H4.