What question did this study set out to answer?

To determine the molecular mechanism by which the candidate tumor suppressor HIC1 recruits corepressor CtBP to mediate transcriptional silencing.

July 1, 2002Molecular and Cellular BiologyOpen Access

The Human Candidate Tumor Suppressor Gene HIC1 Recruits CtBP through a Degenerate GLDLSKK Motif

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Authors

SDSophie DeltourCentre National de la Recherche Scientifique SPSébastien PinteCentre National de la Recherche Scientifique CGCateline GuérardelCentre National de la Recherche Scientifique

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Implication

Molecular analysis demonstrates HIC1 recruits corepressor CtBP via a variant GLDLSKK motif in cell models, indicating dual histone deacetylase-dependent and independent gene silencing mechanisms.

Key Points

To determine the molecular mechanism by which the candidate tumor suppressor HIC1 recruits corepressor CtBP to mediate transcriptional silencing.
Performed cross-species sequence alignment of HIC1 and HRG22 proteins to locate potential corepressor interaction motifs.
Assayed in vivo and in vitro binding between HIC1, its BTB/POZ domain, and mCtBP1.
Measured transcriptional repression using Gal4 DNA-binding domain fusions in the presence and absence of trichostatin A.
Identified a conserved GLDLSKK motif in HIC1 that mediates strong binding to mCtBP1 despite the substitution of an invariant proline for glycine.
Found that while the BTB/POZ domain does not directly contact mCtBP1, BTB/POZ-mediated dimerization is essential for the HIC1–mCtBP1 interaction.
Demonstrated that HIC1 central region repression via CtBP is sensitive to trichostatin A, confirming both HDAC-dependent and HDAC-independent transcriptional repression pathways.

Cite This Study

Deltour et al. (2002) studied this question.

synapsesocial.com/papers/6a7652b83025cdd732bcbf99 https://doi.org/10.1128/mcb.22.13.4890-4901.2002

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Implication

Molecular analysis demonstrates HIC1 recruits corepressor CtBP via a variant GLDLSKK motif in cell models, indicating dual histone deacetylase-dependent and independent gene silencing mechanisms.

The Human Candidate Tumor Suppressor Gene HIC1 Recruits CtBP through a Degenerate GLDLSKK Motif

Discussion

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Implication

Key Points

Cite This Study

The Human Candidate Tumor Suppressor Gene HIC1 Recruits CtBP through a Degenerate GLDLSKK Motif

Discussion

Member takes

Implication

Key Points

Cite This Study

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