A Functional Element Necessary for Fetal Hemoglobin Silencing  

Oleh:

Sankaran, Vijay G. ; Xu, Jian-Xin ; Byron, Rachel ; Greisman, Harvey A.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The New England Journal of Medicine (keterangan: ada di Proquest) vol. 365 no. 09 (Sep. 2011), page 807-814.
Topik: Fetal Hemoglobin

Ketersediaan

Perpustakaan FK Nomor Panggil: N08.K.2011.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

Background An improved understanding of the regulation of the fetal hemoglobin genes holds promise for the development of targeted therapeutic approaches for fetal hemoglobin induction in the ß-hemoglobinopathies. Although recent studies have uncovered trans-acting factors necessary for this regulation, limited insight has been gained into the cis-regulatory elements involved. Methods We identified three families with unusual patterns of hemoglobin expression, suggestive of deletions in the locus of the ß-globin gene (ß-globin locus). We performed array comparative genomic hybridization to map these deletions and confirmed breakpoints by means of polymerase-chain-reaction assays and DNA sequencing. We compared these deletions, along with previously mapped deletions, and studied the trans-acting factors binding to these sites in the ß-globin locus by using chromatin immunoprecipitation. Results We found a new (dß)0-thalassemia deletion and a rare hereditary persistence of fetal hemoglobin deletion with identical downstream breakpoints. Comparison of the two deletions resulted in the identification of a small intergenic region required for ?-globin (fetal hemoglobin) gene silencing. We mapped a Kurdish ß0-thalassemia deletion, which retains the required intergenic region, deletes other surrounding sequences, and maintains fetal hemoglobin silencing. By comparing these deletions and other previously mapped deletions, we elucidated a 3.5-kb intergenic region near the 5' end of the d-globin gene that is necessary for ?-globin silencing. We found that a critical fetal hemoglobin silencing factor, BCL11A, and its partners bind within this region in the chromatin of adult erythroid cells. Conclusions By studying three families with unusual deletions in the ß-globin locus, we identified an intergenic region near the d-globin gene that is necessary for fetal hemoglobin silencing.

Opini Anda

Klik untuk menuliskan opini Anda tentang koleksi ini!

Kembali