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PMID:10428834

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Citation

Nagpal, S, Ghosn, C, DiSepio, D, Molina, Y, Sutter, M, Klein, ES and Chandraratna, RA (1999) Retinoid-dependent recruitment of a histone H1 displacement activity by retinoic acid receptor. J. Biol. Chem. 274:22563-8

Abstract

Targeted recruitment of histone acetyltransferase (HAT) activities by sequence-specific transcription factors, including the retinoic acid receptors (RARs) and retinoid X receptors (RXRs), has been proposed to lead to destabilization of nucleosomal cores by acetylation of core histones. However, biochemical evidence indicates that destabilization and depletion of linker H1 histones must also occur at the promoter regions of actively transcribing genes. Mechanisms by which nuclear receptors and other transcription factors affect the removal of histone H1 from transcriptionally silent chromatin have not been previously described. In this report, we show that RARs interact in a ligand-dependent manner with HMG-I, which is known to displace histone H1 from chromatin. We further show that HMG-I and a novel related protein, HMG-R, also interact with other transcription factors. Using sense and antisense constructs of HMG-I/R in transient transfection assays with a retinoid responsive reporter, we also demonstrate that HMG-I/R is important for retinoid dependent transcriptional activity of RAR. These findings suggest a step wise mechanism by which RARs and other transcription factors can cause a targeted unfolding of compact chromatin as a first step in transcriptional activation, which would then be followed by recruitment of HAT activity and subsequent events.

Links

PubMed

Keywords

Acetylation; Acetyltransferases/metabolism; Amino Acid Sequence; CREB-Binding Protein; Chromatin/metabolism; High Mobility Group Proteins/metabolism; Histone Acetyltransferases; Histones/metabolism; Humans; Ligands; Molecular Sequence Data; Nuclear Proteins/metabolism; Protein Binding; Proto-Oncogene Proteins c-jun/metabolism; Receptors, Cytoplasmic and Nuclear/metabolism; Receptors, Retinoic Acid/metabolism; Retinoid X Receptors; Retinoids/metabolism; Saccharomyces cerevisiae Proteins; Trans-Activators/metabolism; Transcription Factors/metabolism; Transcriptional Activation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:O75798

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P17096

F

Seeded From UniProt

complete

HUMAN:JUN

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P17096

F

Seeded From UniProt

complete

HUMAN:RARG

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P17096

F

Seeded From UniProt

complete

HUMAN:HMGA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P19793

F

Seeded From UniProt

complete

HUMAN:HMGA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75798

F

Seeded From UniProt

complete

HUMAN:HMGA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P37231

F

Seeded From UniProt

complete

HUMAN:HMGA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P13631

F

Seeded From UniProt

complete

HUMAN:HMGA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P05412

F

Seeded From UniProt

complete

HUMAN:HMGA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92793

F

Seeded From UniProt

complete

HUMAN:HMGA1

involved_in

GO:0031936: negative regulation of chromatin silencing

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HMGA1

involved_in

GO:0006337: nucleosome disassembly

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HMGA1

involved_in

GO:0006268: DNA unwinding involved in DNA replication

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HMGA1

enables

GO:0030374: nuclear receptor coactivator activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HMGA1

enables

GO:0001221: transcription coregulator binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HMGA1

enables

GO:0042974: retinoic acid receptor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HMGA1

enables

GO:0042975: peroxisome proliferator activated receptor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HMGA1

enables

GO:0003680: minor groove of adenine-thymine-rich DNA binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HMGA1

part_of

GO:0005667: transcription regulator complex

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HMGA1

enables

GO:0046965: retinoid X receptor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HMGA1

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RXRA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P17096

F

Seeded From UniProt

complete

HUMAN:PPARG

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P17096

F

Seeded From UniProt

complete

HUMAN:CBP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P17096

F

Seeded From UniProt

complete


See also

References

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