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High-Mobility Group or HMG is a group of chromosomal proteins that are involved in the regulation of DNA-dependent processes such as transcription, replication, recombination, and DNA repair.^[1]

Families

The HMG proteins are subdivided into 3 superfamilies each containing a characteristic functional domain:

HMGA – contains an AT-hook domain
- HMGA1
- HMGA2
HMGB – contains a HMG-box domain
- HMGB1
- HMGB2
- HMGB3
- HMGB4
HMGN – contains a nucleosomal binding domain
- HMGN1
- HMGN2
- HMGN3
- HMGN4
- HMGN5

Proteins containing any of these embedded in their sequence are known as HMG motif proteins. HMG-box proteins are found in a variety of eukaryotic organisms.

They were originally isolated from mammalian cells, and named according to their electrophoretic mobility in polyacrylamide gels.^[2]

Other families with HMG-box domain

SOX gene family
- Sex-Determining Region Y Protein
- SOX1, SOX2, etc.
TCF/LEF family (T cell factor/lymphoid enhancer factor family)
- LEF1 (Lymphoid enhancer-binding factor 1)
- TCF7 (TCF-1)
- TCF7L1 (TCF-3)
- TCF7L2 (TCF-4)

Function

HMG proteins are thought to play a significant role in various human disorders. Disruptions and rearrangements in the genes coding for some of the HMG proteins are associated with some common benign tumors. Antibodies to HMG proteins are found in patients with autoimmune diseases. The SRY gene on the Y Chromosome, responsible for male sexual differentiation, contains an HMG-Box domain. A member of the HMG family of proteins, HMGB1, has also been shown to have an extracellular activity as a chemokine, attracting neutrophils and mononuclear inflammatory cells to the infected liver.^[3] The high-mobility group protein such as HMO1 ^[4] alters DNA architecture by binding, bending and looping. Furthermore, these HMG-box DNA-binding proteins increase the flexibility of the DNA upon binding.^[5]

In mammalian cells, the HMG non-histone proteins can modulate the activity of major DNA repair pathways including base excision repair, mismatch repair, nucleotide excision repair and double-strand break repair.^[6]

References

^ Rajeswari MR, Jain A (2002). "High-mobility-group chromosomal proteins, HMGA1 as potential tumour markers" (PDF). Current Science. 82 (7): 838–844.
^ Johns EB (1982). The HMG chromosomal proteins. Boston: Academic Press. ISBN 978-0-12-386050-7.
^ Sitia G, Iannacone M, Müller S, Bianchi ME, Guidotti LG (January 2007). "Treatment with HMGB1 inhibitors diminishes CTL-induced liver disease in HBV transgenic mice". J. Leukoc. Biol. 81 (1): 100–7. doi:10.1189/jlb.0306173. PMID 16935945.
^ Murugesapillai, Divakaran; McCauley, Micah J.; Huo, Ran; Nelson Holte, Molly H.; Stepanyants, Armen; Maher, L. James; Israeloff, Nathan E.; Williams, Mark C. (2014). "DNA bridging and looping by HMO1 provides a mechanism for stabilizing nucleosome-free chromatin". Nucleic Acids Research. 42 (14): 8996–9004. doi:10.1093/nar/gku635. PMC 4132745. PMID 25063301.
^ Murugesapillai, Divakaran; McCauley, Micah J.; Maher, L. James; Williams, Mark C. (2017). "Single-molecule studies of high-mobility group B architectural DNA bending proteins". Biophysical Reviews. 9 (1): 17–40. doi:10.1007/s12551-016-0236-4. PMC 5331113. PMID 28303166.
^ Reeves R. High mobility group (HMG) proteins: Modulators of chromatin structure and DNA repair in mammalian cells. DNA Repair (Amst). 2015 Dec;36:122-136. doi: 10.1016/j.dnarep.2015.09.015. Epub 2015 Sep 16. PMID 26411874