HMGB4 is expressed by neuronal cells and affects the expression of genes involved in neural differentiation

• Published in: Scientific reports Vol. 6; no. 1; p. 32960
• Main Authors: Rouhiainen, Ari, Zhao, Xiang, Vanttola, Päivi, Qian, Kui, Kulesskiy, Evgeny, Kuja-Panula, Juha, Gransalke, Kathleen, Grönholm, Mikaela, Unni, Emmanual, Meistrich, Marvin, Tian, Li, Auvinen, Petri, Rauvala, Heikki
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09-09-2016; Nature Publishing Group
• Subjects: 14/32; 14/35; 45/61; 631/378; 631/80; 82/16; 82/29; 82/51; Animals; Cell death; Cell Line; Chromatin; Chromatin - metabolism; DNA microarrays; Drug screening; Gene Expression Profiling; Gene Expression Regulation; High Mobility Group Proteins - metabolism; Histone H2A; Histone H3; HMGB Proteins - metabolism; Humanities and Social Sciences; Humans; Mice; Microarray Analysis; multidisciplinary; Nervous system; Neurogenesis; Neurons - physiology; Post-translation; Rats; Rodents; Science; Somatic cells; Transformed cells
• DOI: 10.1038/srep32960
• EISSN: 2045-2322

HMGB4 is a new member in the family of HMGB proteins that has been characterized in sperm cells, but little is known about its functions in somatic cells. Here we show that HMGB4 and the highly similar rat Transition Protein 4 (HMGB4L1) are expressed in neuronal cells. Both proteins had slow mobility in nucleus of living NIH-3T3 cells. They interacted with histones and their differential expression in transformed cells of the nervous system altered the post-translational modification statuses of histones
in vitro
. Overexpression of HMGB4 in HEK 293T cells made cells more susceptible to cell death induced by topoisomerase inhibitors in an oncology drug screening array and altered variant composition of histone H3. HMGB4 regulated over 800 genes in HEK 293T cells with a p-value ≤0.013 (n = 3) in a microarray analysis and displayed strongest association with adhesion and histone H2A –processes. In neuronal and transformed cells HMGB4 regulated the expression of an oligodendrocyte marker gene PPP1R14a and other neuronal differentiation marker genes. In conclusion, our data suggests that HMGB4 is a factor that regulates chromatin and expression of neuronal differentiation markers.