Evidence map›Paper›PMID 10891496›Full record

ArticleMolecular and cellular biology2000

Long-distance control of origin choice and replication timing in the human beta-globin locus are independent of the locus control region.

D M Cimbora, D Schübeler, A Reik, J Hamilton, C Francastel, E M Epner, M Groudine

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 114 citations in OpenAlex.

  1. Article
  2. Review
  3. TheProceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  4. Control of DNA replication timing in the 3D genome.Nature reviews. Molecular cell biology · 2019
    Review
  5. Article
  6. Article
  7. Maintenance of Epigenetic Information.Cold Spring Harbor perspectives in biology · 2016
    Review
  8. Altered histone modifications in gliomas.Brain tumor research and treatment · 2014
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Domain-wide regulation of DNA replication timing during mammalian development.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2010
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

D M CimboraDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
D Schübeler
A Reik
J Hamilton
C Francastel
E M Epner
M Groudine
Fred Hutch Cancer Center · USUniversity of Arizona · USUniversity of Washington Medical Center · US

Funding

FUNCTION OF HUMAN &MOUSE B GLOBIN LOCUS CONTROL REGIONSR37DK044746 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GROUDINE, MARK T · 1997 to 2016
$12.3M
C-MYC PROTO-ONCOGENE TRANSCRIPTIONAL ELONGATION BLOCKR01CA054337 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GROUDINE, MARK T · 1991 to 2000
$550k
FUNCTION OF THE HUMAN B-GLOBIN LOCUS CONTROL REGION-LCRR01DK044746 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GROUDINE, MARK T · 1992 to 1996
–
MAINTENANCE AND REGULATION OF GLOBIN GENE EXPRESSIONR01HL057620 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GROUDINE, MARK T · 1996 to 1999
–
NCI NIH HHS CA54337NHLBI NIH HHS HL57620NIDDK NIH HHS DK44746NIDDK NIH HHS R37 DK044746
6 · The paper itself

Abstract

DNA replication in the human beta-globin locus is subject to long-distance regulation. In murine and human erythroid cells, the human locus replicates in early S phase from a bidirectional origin located near the beta-globin gene. This Hispanic thalassemia deletion removes regulatory sequences located over 52 kb from the origin, resulting in replication of the locus from a different origin, a shift in replication timing to late S phase, adoption of a closed chromatin conformation, and silencing of globin gene expression in murine erythroid cells. The sequences deleted include nuclease-hypersensitive sites 2 to 5 (5'HS2-5) of the locus control region (LCR) plus an additional 27-kb upstream region. We tested a targeted deletion of 5'HS2-5 in the normal chromosomal context of the human beta-globin locus to determine the role of these elements in replication origin choice and replication timing. We demonstrate that the 5'HS2-5-deleted locus initiates replication at the appropriate origin and with normal timing in murine erythroid cells, and therefore we conclude that 5'HS2-5 in the classically defined LCR do not control replication in the human beta-globin locus. Recent studies also show that targeted deletion of 5'HS2-5 results in a locus that lacks globin gene expression yet retains an open chromatin conformation. Thus, the replication timing of the locus is closely correlated with nuclease sensitivity but not globin gene expression.

Indexed as

DNA ReplicationReplication OriginAnimalsCell LineDeoxyribonuclease IErythroid Precursor CellsGlobinsHumansMiceSequence DeletionTime FactorsDeoxyribonuclease IGlobins

Identifiers

PMID10891496
PMCPMC86017
OpenAlexW2129416152

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.