Several cofactors, such as coactivators steroid receptor coactivator 1 (SRC1), transcriptional mediators/intermediary factor 2, SRC3 and corepressors
nuclear receptor-interacting protein 1, nuclear receptor subfamily 0 group B member 1, are actively involved in the regulation of AR-mediated transcription, and might play an important role in AIS etiopathogenesis (12,13,14,15).
It can also inhibit transcription factors (e.g., histone lysine-specific demethylase, promyelocytic leukemia zinc finger and B-Cell CLL/Lymphoma 6) [7-9] leading to inhibition of the transcriptional activity of related genes, mainly by the recruitment of transcriptional corepressors
(e.g., nuclear receptor corepressor
and its homolog SMRT, mSi3a [component of histone deacetylase complex], histone deacetylase) via its homodimeric domain [10-12].
In particular, characterizing the interactions of corepressors
in the pathway provides valuable information about regulation of Notch signaling.
Mandel, "REST and its corepressors
mediate plasticity of neuronal gene chromatin throughout neurogenesis," Cell, vol.
Tsai, "Histone deacetylase-associating Atrophin proteins are nuclear receptor corepressors
," Genes and Development, vol.
Whether a SERM is effective as an ER agonist or antagonist in a particular tissue depends upon several factors including the ER subtypes present, conformation of the ERs induced by the SERM, level, types, availability of coactivators and corepressors
in the tissue, and types of coactivators and/or corepressors
recruited to form the ER complex and the degree of interactions [22,29, 111-114].
HDACs can participate in gene silencing due to their binding to MeCP2 along with other corepressors
, such as mSin3A [20, 21, 55].
In the nucleus, SMADs can interact with an increasing number of transcription factors, transcriptional coactivators, or transcriptional corepressors
Baldwin Jr., "The p65 (RelA) subunit of NF-[kappa]B interacts with the histone deacetylase (HDAC) corepressors
HDAC1 and HDAC2 to negatively regulate gene expression," Molecular and Cellular Biology, vol.
During unstimulated conditions, the heterodimer complex is associated with corepressors
(NCoR and SMRT), which suppress gene transcription .
Conversely, HDACs, as transcription corepressors
, remove the acetyl groups from the acetylated lysines in histones .
Other studies designed to identify potential SS18-SSX binding partners revealed that SS18-SSX acts as a bridge between the transcription corepressors
ATF2 and TLE1, thereby down-regulating ATF3, EGR1, and CDKN2A.