HMGB4 is expressed by neuronal cells and affects the expression of genes involved in neural differentiation.
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.
Neuroscience center, University of Helsinki, Finland.|Department of Biosciences, University of Helsinki, Finland.
Ari
A
Rouhiainen
Neuroscience center, University of Helsinki, Finland.|Schools of Pharmacy and Medicine, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, USA.
Xiang
X
Zhao
Neuroscience center, University of Helsinki, Finland.
Päivi
P
Vanttola
Institute of Biotechnology, University of Helsinki, Finland.
Kui
K
Qian
Neuroscience center, University of Helsinki, Finland.|Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Finland.
Evgeny
E
Kulesskiy
Neuroscience center, University of Helsinki, Finland.
Juha
J
Kuja-Panula
Neuroscience center, University of Helsinki, Finland.
Kathleen
K
Gransalke
Department of Biosciences, University of Helsinki, Finland.
Mikaela
M
Grönholm
Department of Biochemistry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Emmanual
E
Unni
Department of Experimental Radiation Oncology, Division of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas, USA.
Marvin
M
Meistrich
Neuroscience center, University of Helsinki, Finland.|Psychiatry Research Center, Beijing Hui Long Guan Hospital, Peking University, Beijing, China.
Li
L
Tian
Institute of Biotechnology, University of Helsinki, Finland.
Petri
P
Auvinen
Neuroscience center, University of Helsinki, Finland.
Heikki
H
Rauvala
D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D024002:HMGB Proteins / Q000378:metabolism*; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D046228:Microarray Analysis; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology*; D051381:Rats
D002843:Chromatin; D024002:HMGB Proteins; C539347:HMGB4 protein, mouse; D006609:High Mobility Group Proteins; C000627677:LOC103694517 protein, rat