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Record W7049014092

Molecular basis for the role of GATA transcription factors in cardiomyocytes

2001· dissertation· en· W7049014092 on OpenAlexfundno aff

Bibliographic record

VenueeScholarship@McGill (McGill) · 2001
Typedissertation
Languageen
FieldPhysics and Astronomy
TopicCrystallography and Radiation Phenomena
Canadian institutionsnot available
FundersMedical Research CouncilCanadian Institutes of Health ResearchNational Cancer InstituteNational Institutes of HealthNatural Sciences and Engineering Research Council of CanadaHeart and Stroke Foundation of Canada
KeywordsGATA4Mef2Zinc fingerTranscription factorGATA transcription factorGeneGATA2MEF2CRegulation of gene expression
DOInot available

Abstract

fetched live from OpenAlex

Members of the GATA family of transcription factors are evolutionary conserved DNA-binding proteins that play critical roles in cell differentiation. They share a highly conserved zinc finger domain responsible for specific binding to a consensus (A/T)GATA(A/G) sequence. Three GATA factors, GATA-4, GATA-5, and GATA-6, are expressed in the heart and two of them, GATA-4 and GATA-6, are coexpressed in cardiomyocytes. Given the early embryonic lethality of GATA-4 and GATA-6 null mice, their exact role in cardiomyocytes was unclear. The objective of my doctoral work was to elucidate the role of GATA-4 and GATA-6 in postnatal cardiomyocytes and the molecular basis for their specificity. Since the identification of GATA-4 and GATA-6 target genes would help to elucidate their functions, we inhibited GATA-4 and GATA-6 protein production in postnatal cardiomyocytes and assessed its effect on cardiac gene expression. The results demonstrated that GATA-4 and GATA-6 are required for the maintenance of cardiac gene expression. Importantly, the work showed that GATA-4 and GATA-6 differentially regulate target genes and that this specificity is due, at least in part, to their differential DNA-binding affinity. In addition to differential DNA-binding affinity, we showed that GATA factors also acquire specificity by differential interaction with cofactors, such as MEF2 and Nkx2-5. Thus, GATA factor specificity is achieved at three levels: differential spatio-temporal expression, differential DNA-binding affinity, and differential interaction with cofactors.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.237
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.222
Teacher spread0.213 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2001
Admission routes1
Has abstractyes

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