Evidence map›Paper›PMID 15252056›Full record

ArticleThe Journal of biological chemistry2004

The HoxC4 homeodomain protein mediates activation of the immunoglobulin heavy chain 3' hs1,2 enhancer in human B cells. Relevance to class switch DNA recombination.

Edmund C Kim, Christopher R Edmonston, Xiaoping Wu, András Schaffer, Paolo Casali

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

18 citing papers in PubMed, 32 citations in OpenAlex.

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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

5 authors at 1 institution in 1 country.

Edmund C KimCenter for Immunology, College of Medicine and School of Biological Sciences, University of California, Irvine, California 92697-4120, USA.
Christopher R Edmonston
Xiaoping Wu
András Schaffer
Paolo Casali
University of California, Irvine · US

Funding

Immunoglobulin class switch DNA recombinationR01AI045011 · NIAID · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI CASALI, PAOLO · 2000 to 2011
$3.8M
SOMATIC HYPERMUTATION IN HUMAN B CELLSR01AR040908 · NIAMS · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI CASALI, PAOLO · 1992 to 2005
$1.8M
Immunoglobulin class switch DNA recombinationR56AI045011 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI CASALI, PAOLO · 2012 to 2012
$523k
NIAID NIH HHS AI 45011NIAID NIH HHS R01 AI045011NIAID NIH HHS R56 AI045011NIAMS NIH HHS AR 40908NIAMS NIH HHS R01 AR040908
6 · The paper itself

Abstract

The immunoglobulin heavy chain (IgH) 3' regulatory region modulates IgH locus transcription, upon induction by specific trans-acting factors, and plays a significant role in class switch DNA recombination (CSR) and, perhaps, somatic hypermutation (SHM). CSR and SHM are central to the maturation of the antibody response. In contrast to the single 5'-hs3a-hs1,2-hs3b-hs4-3 ' mouse IgH 3 ' regulatory region, the human IgH 3 ' regulatory region exists as a 5'-hs3-hs1,2-hs4-3' cluster duplicated 3 ' of Calpha1 and Calpha2. We show here that the human hs1,2 element is the strongest enhancer of transcription, as directed by a V(H)1 or the ECS-Igamma3 promoter, thereby suggesting a dominant role for hs1,2 over hs3 and hs4 in the overall activity of the 3 ' regulatory region. Within hs1,2, we identified three regions (1, 2, and 3) that are all necessary, but individually not sufficient, for enhancement of transcription. In region 2, a HoxC4 site and a HoxC4/embedded octamer (HoxC4/Oct) site are conserved across human, mouse, rat, and rabbit. These two sites recruit HoxC4 and Oct-1/Oct-2, which act synergistically with the Oca-B coactivator to effect the full hs1,2-enhancing activity. HoxC4, Oct-1/Oct-2, and Oca-B recruitment is negligible in pro-B cells, moderate in pre-B cells, and maximal in germinal center B cells and plasma cells, where HoxC4, Oct-2, and Oca-B expression correlates with hs1,2 activation and ongoing CSR. The hs1,2mediated enhancement of V(H) and C(H) promoter-driven transcription as induced by HoxC4 and Oct-1/Oct-2 suggests an important role of these homeodomain proteins in the overall regulation of the IgH locus expression.

Indexed as

Genes, RegulatorTranscriptional Activation3' Flanking RegionB-LymphocytesConserved SequenceDNA-Binding ProteinsHomeodomain ProteinsHumansImmunoglobulin Heavy ChainsOctamer Transcription Factor-1Octamer Transcription Factor-2Trans-ActivatorsTranscription FactorsDNA-Binding ProteinsHomeodomain ProteinsHOXC4 protein, humanHoxc4 protein, mouseImmunoglobulin Heavy ChainsOctamer Transcription Factor-1Octamer Transcription Factor-2POU2AF1 protein, humanPou2af1 protein, mousePOU2F1 protein, humanPOU2F2 protein, humanPou2f2 protein, mousePou2f2 protein, ratTrans-ActivatorsTranscription Factors

Identifiers

PMID15252056
PMCPMC4631311
OpenAlexW2033976924

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.