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Gene Review:

HPFH2 - hereditary persistence of fetal hemoglobin...

Homo sapiens

Poncz, M. et al., Xiang, P. et al., Elder, J.T. et al., Katsantoni, E.Z. et al., Vives-Corrons, J.L. et al., et al.

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Disease relevance of HPFH2

The Spanish type of delta beta-thalassemia is a mild thalassemic condition due to a large deletion starting at the Alu I repeat between the A gamma and delta-globin genes immediately 3' to the RIH probe and extending 11 and 17 kb downstream of the 3' endpoints of HPFH 1 and HPFH 2, respectively [1].
Genomic DNA purified from nucleated red blood cells (nRBC) from a patient with HPFH-2/beta O thalassemia was digested with Msp I or Hpa II, and the methylation pattern determined on the HPFH chromosome by using secondary cleavage with restriction enzymes which span the deletion breakpoint [2].

High impact information on HPFH2

The failure of gamma-gene reactivation by the juxtaposed HPFH2 enhancer contradicts the results of previous studies [3].
Juxtaposition of the HPFH2 enhancer is not sufficient to reactivate the gamma-globin gene in adult erythropoiesis [3].
To test the hypothesis in a much stricter basis, we produced beta locus YAC transgenic mice carrying an exact beta locus replicate of a deletional HPFH mutation, HPFH 2 [3].
Cre-mediated generation of single copy lines showed persistent gamma gene expression maintained in some of the HPFH-2 and HPFH-6 lines, but not in any of the HPFH-3 or LCRA gamma lines [4].
In the HPFH-2 and HPFH-6 lines, persistent gamma gene expression correlated with euchromatic transgene integrations [4].

Biological context of HPFH2

These results indicate that breakpoint DNA sequences in deletion-type HPFH-2 can modify the developmentally regulated expression of the gamma-globin genes [5].
As predicted by the locations of the deletion endpoints, the first two sites were translocated to within 12 kb of the A gamma gene in erythroid colonies derived from an HPFH-2 heterozygote and in hybrid mouse-human erythroid cells carrying the HPFH-2 deletion chromosome [6].
These studies show that in nRBC the HPFH-2 chromosome is hypomethylated in the 3'-juxtaposed region (3'JR) and in the region of the gamma-globin genes [2].
DNA methylation in hereditary persistence of fetal hemoglobin (HPFH-2) [2].
One member of this family is found downstream of the beta-globin gene cluster between the 3' breakpoints of the deletions associated with Chinese G gamma + (A gamma delta beta)O thalassemia and HPFH-2 [7].

Anatomical context of HPFH2

A third site, most prominent in fetal liver-derived erythroid cells, was found 1 kb upstream of the HPFH-2 deletion endpoint [6].

Other interactions of HPFH2

In contrast, Msp I sites near the truncated psi beta-globin gene remain methylated, suggesting that only a subset of CpG sites upstream from the 3'JR become hypomethylated in HPFH-2 [2].

References

Rapid detection of Spanish (delta beta)zero-thalassemia deletion by polymerase chain reaction. Vives-Corrons, J.L., Pujades, M.A., Miguel-García, A., Miguel-Sosa, A., Cambiazzo, S. Blood (1992) [Pubmed]
DNA methylation in hereditary persistence of fetal hemoglobin (HPFH-2). Poncz, M., Sutton, M., Delgrosso, K., Schwartz, E., Surrey, S. Nucleic Acids Res. (1987) [Pubmed]
Juxtaposition of the HPFH2 enhancer is not sufficient to reactivate the gamma-globin gene in adult erythropoiesis. Xiang, P., Han, H., Barkess, G., Olave, I., Fang, X., Yin, W., Stamatoyannopoulos, G., Li, Q. Hum. Mol. Genet. (2005) [Pubmed]
Persistent gamma-globin expression in adult transgenic mice is mediated by HPFH-2, HPFH-3, and HPFH-6 breakpoint sequences. Katsantoni, E.Z., Langeveld, A., Wai, A.W., Drabek, D., Grosveld, F., Anagnou, N.P., Strouboulis, J. Blood (2003) [Pubmed]
High levels of human gamma-globin gene expression in adult mice carrying a transgene of deletion-type hereditary persistence of fetal hemoglobin. Arcasoy, M.O., Romana, M., Fabry, M.E., Skarpidi, E., Nagel, R.L., Forget, B.G. Mol. Cell. Biol. (1997) [Pubmed]
Translocation of an erythroid-specific hypersensitive site in deletion-type hereditary persistence of fetal hemoglobin. Elder, J.T., Forrester, W.C., Thompson, C., Mager, D., Henthorn, P., Peretz, M., Papayannopoulou, T., Groudine, M. Mol. Cell. Biol. (1990) [Pubmed]
A retrovirus-like element occurs between the 3' breakpoints of two large deletions in the human beta-globin gene cluster. Mager, D.L., Henthorn, P.S. Prog. Clin. Biol. Res. (1985) [Pubmed]

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