HMGA is a family of high mobility group proteins characterized by an AT-hook. They code for a "small, nonhistone, chromatin-associated protein that has no intrinsic transcriptional activity but can modulate transcription by altering the chromatin architecture".[1] Mammals have two orthologs: HMGA1 and HMGA2.

high mobility group AT-hook 1
Identifiers
SymbolHMGA1
Alt. symbolsHMGIY
NCBI gene3159
HGNC5010
OMIM600701
RefSeqNM_145901
UniProtP17096
Other data
LocusChr. 6 p21
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StructuresSwiss-model
DomainsInterPro
high mobility group AT-hook 2
Identifiers
SymbolHMGA2
Alt. symbolsHMGIC
NCBI gene8091
HGNC5009
OMIM600698
RefSeqNM_003484
UniProtP52926
Other data
LocusChr. 12 q15
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StructuresSwiss-model
DomainsInterPro

Genomic distribution

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In mouse embryonic stem cells it has been demonstrated that both HMGA proteins binds uniformly to the DNA due to their AT-hook domains, with a slight preference for AT-rich regions/[2] Such regions tend to lack coding genes, an observation that argues against a direct role in transcriptional control and in agreement with previous studies, suggest that these proteins have a structural role in the chromatin, similar to histone.

Function

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Normally, when cells are subjected to increased DNA damage (such as the formation of 6-O-methylguanine) this causes an increase in apoptosis (programmed cell death). However, cells with diminished activity for either proteins HMGA1 or HMGA2 (or both together) are more tolerant of such DNA damage than cells in which these proteins are not diminished.[3] Thus a normal function of the HMGA1 and HMGA2 proteins appears to be to signal the presence of DNA damage leading to induction of apoptosis.[3]

Association with human traits

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Variations in HMGA2 to have a moderate association with adult height.[4][5]

See also

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References

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  1. ^ Mayr C, Hemann MT, Bartel DP (March 2007). "Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation". Science. 315 (5818): 1576–1579. Bibcode:2007Sci...315.1576M. doi:10.1126/science.1137999. PMC 2556962. PMID 17322030.
  2. ^ Colombo DF, Burger L, Baubec T, Schübeler D (December 2017). "Binding of high mobility group A proteins to the mammalian genome occurs as a function of AT-content". PLOS Genetics. 13 (12): e1007102. doi:10.1371/journal.pgen.1007102. PMC 5756049. PMID 29267285.
  3. ^ a b Fujikane R, Komori K, Sekiguchi M, Hidaka M (August 2016). "Function of high-mobility group A proteins in the DNA damage signaling for the induction of apoptosis". Scientific Reports. 6: 31714. Bibcode:2016NatSR...631714F. doi:10.1038/srep31714. PMC 4990841. PMID 27538817.
  4. ^ "Scientists discover height gene". BBC News. 2007-09-03. Retrieved 2007-09-03.
  5. ^ Weedon MN, Lettre G, Freathy RM, Lindgren CM, Voight BF, Perry JR, et al. (October 2007). "A common variant of HMGA2 is associated with adult and childhood height in the general population". Nature Genetics. 39 (10): 1245–1250. doi:10.1038/ng2121. PMC 3086278. PMID 17767157.
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