Abstract
Retinoid receptors behave as ligand-dependent transcriptional regulators, repressing transcription in the absence of ligand and activating transcription in its presence. The different effects on transcription are carried out through recruitment of co-regulators: unliganded receptors bind compressors (NCoR and SMRT) that are found within a complex containing histone deacetylase (HDAC) activity, whereas liganded receptors recruit coactivators with histone acetylase activity (HATs). Chromatin remodeling activities have also shown to be required, suggesting a hierarchy of promoter structure modifications in RA target genes carried out by multiple coregulatory complexes. In this review, we examine the experimental evidence for the model just sketched. We focus on recent findings highlighting new molecular details in receptor-coregulator interactions, including the discovery and initial characterisation of novel complexes with multiple chromatin modifying activities. Finally, we look at the role of aberrant recruitment of the NCoR-HDAC complex by altered retinoid receptors in the pathogenesis of acute promyelocytic leukemia. These results point to a crucial role for control of transcription factor-coregulator interactions in the regulation of cellular processes, and suggest new molecular targets for cancer therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 215-225 |
| Number of pages | 11 |
| Journal | Seminars in Cell and Developmental Biology |
| Volume | 10 |
| Issue number | 2 |
| Publication status | Published - Apr 1999 |
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Keywords
- Histone acetylation
- Nuclear co-activators
- Nuclear co-repressors
- Retinoids
- RXR-RAR heterodimers
ASJC Scopus subject areas
- Developmental Biology
Cite this
Retinoid receptors in health and disease : Co-regulators and the chromatin connection. / Minucci, Saverio; Pelicci, Pier Giuseppe.
In: Seminars in Cell and Developmental Biology, Vol. 10, No. 2, 04.1999, p. 215-225.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Retinoid receptors in health and disease
T2 - Co-regulators and the chromatin connection
AU - Minucci, Saverio
AU - Pelicci, Pier Giuseppe
PY - 1999/4
Y1 - 1999/4
N2 - Retinoid receptors behave as ligand-dependent transcriptional regulators, repressing transcription in the absence of ligand and activating transcription in its presence. The different effects on transcription are carried out through recruitment of co-regulators: unliganded receptors bind compressors (NCoR and SMRT) that are found within a complex containing histone deacetylase (HDAC) activity, whereas liganded receptors recruit coactivators with histone acetylase activity (HATs). Chromatin remodeling activities have also shown to be required, suggesting a hierarchy of promoter structure modifications in RA target genes carried out by multiple coregulatory complexes. In this review, we examine the experimental evidence for the model just sketched. We focus on recent findings highlighting new molecular details in receptor-coregulator interactions, including the discovery and initial characterisation of novel complexes with multiple chromatin modifying activities. Finally, we look at the role of aberrant recruitment of the NCoR-HDAC complex by altered retinoid receptors in the pathogenesis of acute promyelocytic leukemia. These results point to a crucial role for control of transcription factor-coregulator interactions in the regulation of cellular processes, and suggest new molecular targets for cancer therapy.
AB - Retinoid receptors behave as ligand-dependent transcriptional regulators, repressing transcription in the absence of ligand and activating transcription in its presence. The different effects on transcription are carried out through recruitment of co-regulators: unliganded receptors bind compressors (NCoR and SMRT) that are found within a complex containing histone deacetylase (HDAC) activity, whereas liganded receptors recruit coactivators with histone acetylase activity (HATs). Chromatin remodeling activities have also shown to be required, suggesting a hierarchy of promoter structure modifications in RA target genes carried out by multiple coregulatory complexes. In this review, we examine the experimental evidence for the model just sketched. We focus on recent findings highlighting new molecular details in receptor-coregulator interactions, including the discovery and initial characterisation of novel complexes with multiple chromatin modifying activities. Finally, we look at the role of aberrant recruitment of the NCoR-HDAC complex by altered retinoid receptors in the pathogenesis of acute promyelocytic leukemia. These results point to a crucial role for control of transcription factor-coregulator interactions in the regulation of cellular processes, and suggest new molecular targets for cancer therapy.
KW - Histone acetylation
KW - Nuclear co-activators
KW - Nuclear co-repressors
KW - Retinoids
KW - RXR-RAR heterodimers
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M3 - Article
C2 - 10441075
AN - SCOPUS:0033109775
VL - 10
SP - 215
EP - 225
JO - Seminars in Cell and Developmental Biology
JF - Seminars in Cell and Developmental Biology
SN - 1084-9521
IS - 2
ER -