Advanced

ABO transcript levels in peripheral blood and erythropoietic culture show different allele-related patterns independent of the CBF/NF-Y enhancer motif and multiple novel allele-specific variations in the 5'- and 3'-noncoding regions.

Thuresson, Britt LU ; Chester, Alan LU ; Storry, Jill LU and Olsson, Martin L LU (2008) In Transfusion 48(3). p.493-504
Abstract
BACKGROUND: Mechanisms regulating the ABO gene are unclear, especially in the hematopoietic compartment. The number of 43-bp repeats in the CBF/NF-Y-binding enhancer region is considered to have a major influence on transcription. STUDY DESIGN AND METHODS: Transcript levels in peripheral blood and in erythropoietic culture of CD34+ cells from marrow donors were measured with TaqMan assays. The 5'-regulatory region and 3'-downstream sequences were investigated to determine if allelic variations occur. RESULTS: Surprisingly, transcripts from A(1) and A(2) alleles could not be detected in peripheral blood, although transcripts from B/O(1)/O(1v)/O(2) alleles were readily observed. Sequencing of approximately 4 kb upstream and 1.8 kb downstream... (More)
BACKGROUND: Mechanisms regulating the ABO gene are unclear, especially in the hematopoietic compartment. The number of 43-bp repeats in the CBF/NF-Y-binding enhancer region is considered to have a major influence on transcription. STUDY DESIGN AND METHODS: Transcript levels in peripheral blood and in erythropoietic culture of CD34+ cells from marrow donors were measured with TaqMan assays. The 5'-regulatory region and 3'-downstream sequences were investigated to determine if allelic variations occur. RESULTS: Surprisingly, transcripts from A(1) and A(2) alleles could not be detected in peripheral blood, although transcripts from B/O(1)/O(1v)/O(2) alleles were readily observed. Sequencing of approximately 4 kb upstream and 1.8 kb downstream of the coding region showed multiple novel allele-specific and allele-related motifs. No correlation between these sequence variations and transcript levels was found, however. Contradictory to the results with peripheral blood, in erythropoietic culture of CD34+ cells from healthy marrow donors transcripts from A(1) and A(2) alleles were found at higher levels than transcripts from B/O(1)/O(1v) alleles. CONCLUSION: These data do not support previous suggestions that nonsense-mutated O(1)/O(1v) transcripts are eliminated first. Furthermore, our results contradict the notion that the number of repeats in the upstream CBF/NF-Y-binding enhancer region, which contains four 43-bp repeats in A(2)/B/O(1)/O(1v) but only one 43-bp unit in A(1)/O(2) alleles, determines the transcription rate. The reason for the remarkable discrepancy between blood and marrow remains to be elucidated. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Transfusion
volume
48
issue
3
pages
493 - 504
publisher
Wiley-Blackwell
external identifiers
  • pmid:18067502
  • wos:000253484900013
  • scopus:39749088868
ISSN
1537-2995
DOI
10.1111/j.1537-2995.2007.01554.x
language
English
LU publication?
yes
id
cd8c109e-cde4-495d-8874-8a68924ab93d (old id 1035478)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18067502?dopt=Abstract
date added to LUP
2008-09-09 09:34:36
date last changed
2017-01-01 06:18:01
@article{cd8c109e-cde4-495d-8874-8a68924ab93d,
  abstract     = {BACKGROUND: Mechanisms regulating the ABO gene are unclear, especially in the hematopoietic compartment. The number of 43-bp repeats in the CBF/NF-Y-binding enhancer region is considered to have a major influence on transcription. STUDY DESIGN AND METHODS: Transcript levels in peripheral blood and in erythropoietic culture of CD34+ cells from marrow donors were measured with TaqMan assays. The 5'-regulatory region and 3'-downstream sequences were investigated to determine if allelic variations occur. RESULTS: Surprisingly, transcripts from A(1) and A(2) alleles could not be detected in peripheral blood, although transcripts from B/O(1)/O(1v)/O(2) alleles were readily observed. Sequencing of approximately 4 kb upstream and 1.8 kb downstream of the coding region showed multiple novel allele-specific and allele-related motifs. No correlation between these sequence variations and transcript levels was found, however. Contradictory to the results with peripheral blood, in erythropoietic culture of CD34+ cells from healthy marrow donors transcripts from A(1) and A(2) alleles were found at higher levels than transcripts from B/O(1)/O(1v) alleles. CONCLUSION: These data do not support previous suggestions that nonsense-mutated O(1)/O(1v) transcripts are eliminated first. Furthermore, our results contradict the notion that the number of repeats in the upstream CBF/NF-Y-binding enhancer region, which contains four 43-bp repeats in A(2)/B/O(1)/O(1v) but only one 43-bp unit in A(1)/O(2) alleles, determines the transcription rate. The reason for the remarkable discrepancy between blood and marrow remains to be elucidated.},
  author       = {Thuresson, Britt and Chester, Alan and Storry, Jill and Olsson, Martin L},
  issn         = {1537-2995},
  language     = {eng},
  number       = {3},
  pages        = {493--504},
  publisher    = {Wiley-Blackwell},
  series       = {Transfusion},
  title        = {ABO transcript levels in peripheral blood and erythropoietic culture show different allele-related patterns independent of the CBF/NF-Y enhancer motif and multiple novel allele-specific variations in the 5'- and 3'-noncoding regions.},
  url          = {http://dx.doi.org/10.1111/j.1537-2995.2007.01554.x},
  volume       = {48},
  year         = {2008},
}