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:
https://lup.lub.lu.se/record/1035478
- author
- Thuresson, Britt
LU
; Chester, Alan
LU
; Storry, Jill
LU
and Olsson, Martin L
LU
- organization
- publishing date
- 2008
- 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
- pmid:18067502
- 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
- 2016-04-01 14:33:03
- date last changed
- 2022-01-28 01:13:54
@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}},
doi = {{10.1111/j.1537-2995.2007.01554.x}},
volume = {{48}},
year = {{2008}},
}