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The High Mobility Group Protein HMGA2: A Co-Regulator of Chromatin Structure and Pluripotency in Stem Cells?
- Source :
- Stem Cell Reviews and Reports. 5:224-230
- Publication Year :
- 2009
- Publisher :
- Springer Science and Business Media LLC, 2009.
-
Abstract
- The small, chromatin-associated HMGA proteins contain three separate DNA binding domains, so-called AT hooks, which bind preferentially to short AT-rich sequences. These proteins are abundant in pluripotent embryonic stem (ES) cells and most malignant human tumors, but are not detectable in normal somatic cells. They act both as activator and repressor of gene expression, and most likely facilitate DNA architectural changes during formation of specialized nucleoprotein structures at selected promoter regions. For example, HMGA2 is involved in transcriptional activation of certain cell proliferation genes, which likely contributes to its well-established oncogenic potential during tumor formation. However, surprisingly little is known about how HMGA proteins bind DNA packaged in chromatin and how this affects the chromatin structure at a larger scale. Experimental evidence suggests that HMGA2 competes with binding of histone H1 in the chromatin fiber. This could substantially alter chromatin domain structures in ES cells and contribute to the activation of certain transcription networks. HMGA2 also seems capable of recruiting enzymes directly involved in histone modifications to trigger gene expression. Furthermore, it was shown that multiple HMGA2 molecules bind stably to a single nucleosome core particle whose structure is known. How these features of HMGA2 impinge on chromatin organization inside a living cell is unknown. In this commentary, we propose that HMGA2, through the action of three independent DNA binding domains, substantially contributes to the plasticity of ES cell chromatin and is involved in the maintenance of a un-differentiated cell state.
- Subjects :
- Pluripotent Stem Cells
Cancer Research
Transcription, Genetic
Molecular Sequence Data
Molecular Conformation
Biology
Chromatin remodeling
Histones
Mice
Animals
Humans
Histone code
Amino Acid Sequence
ChIA-PET
Chromatin Fiber
Stem Cells
HMGA2 Protein
DNA
Cell Biology
ChIP-on-chip
Molecular biology
Chromatin
Protein Structure, Tertiary
ChIP-sequencing
Cell biology
Gene Expression Regulation
Bivalent chromatin
Subjects
Details
- ISSN :
- 15586804 and 15508943
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Stem Cell Reviews and Reports
- Accession number :
- edsair.doi.dedup.....48df0850d791c91beb390a6dedf572e6
- Full Text :
- https://doi.org/10.1007/s12015-009-9078-9