High mobility group box 1 protein, also known as high-mobility group protein 1 (HMG-1) and amphoterin, is a protein that in humans is encoded by the HMGB1 gene. Like the histones, HMGB1 is among the most important chromatin proteins. In the nucleus HMGB1 interacts with nucleosomes, transcription factors, and histones. This nuclear protein organizes the DNA and regulates transcription. After binding, HMGB1 bends DNA, which facilitates the binding of other proteins. HMGB1 supports transcription of many genes in interactions with many transcription factors. It also interacts with nucleosomes to loosen packed DNA and remodel the chromatin. Contact with core histones changes the structure of nucleosomes. HMGB1 can be secreted by immune cells (like macrophages, monocytes and dendritic cells) through leaderless secretory pathway. Activated macrophages and monocytes secrete HMGB1 as a cytokine mediator of Inflammation.