Nuclear receptors and chromatin: an inducible couple

Abstract

The nuclear receptor (NR) family comprises 48 transcription factors (TFs) with essential and diverse roles in development, metabolism and disease. Differently from other TFs, NRs engage with well-defined DNA-regulatory elements, mostly after ligand-induced structural changes. However, NR binding is not stochastic, and only a fraction of the cognate regulatory elements within the genome actively engage with NRs. In this review, we summarize recent advances in the understanding of the interactions between NRs and DNA. We discuss how chromatin accessibility and epigenetic modifications contribute to the recruitment and transactivation of NRs. Lastly, we present novel evidence of the interplay between non-coding RNA and NRs in the mediation of the assembly of the transcriptional machinery.

Regulation of TRH neurons and energy homeostasis-related signals under stress

“…Chromatin remodeling constitutes the first step in transcriptional regulation; recruitment of specific TF, coregulators, and histone acetylases loosens the DNA from histones allowing initiation of transcription by RNA polymerase II (Pol II ; Fig. 3B); certain TFs recruit histone deacetylases that compact chromatin repressing transcription (Gadaleta & Magnani 2014; Fig. 3C).…”

“…Cell lines are homogenous but with a particular set up that differs from the physiological situation, they are usually incubated with drugs for long periods and under steady conditions in contrast to in vivo situations where events such as clearance and diffusion play important roles. Transient transfections omit the regulatory steps related to chromatin remodeling (Gadaleta & Magnani 2014). Primary culture of embryonic hypothalamic cells (Uribe et al 1995a, Harris et al 2001, or transfected hypothalami of newborn pups (Guissouma et al 2000), involve a mixture of multiple hypothalamic nuclei whose developmental windows, afferents and receptors, might differ to those exclusive to the PVN; furthermore, they miss the developmental effects of gonadal hormones (McCutcheon & Marinelli 2009 manipulation of many organs that contribute, for example, to altered TH levels (Astapova & Hollenberg 2013); however, they revealed the redundancy of important regulatory molecules (Chiappini et al 2013).…”

MicroRNA: sex steroids, hormonal carcinogenesis, hormonal sensitivity of tumor tissue

“…Стероидные рецепторы способны непосредственно взаимодействовать с опре-деленными участками геномной ДНК и активиро-вать / блокировать транскрипцию таргетных генов [16]. Аналогичным образом опосредуется и один из основ-ных известных путей гормонозависимой регуляции транскрипции генов, кодирующих микроРНК [6].…”

Noncoding RNAs and the control of hormonal signaling via nuclear receptor regulation

“…The transcription of regulated genes is modulated by co-binding of an array of co-factors as well as RNA polymerases and several components of the transcription initiation machinery (Acevedo & Kraus 2004, Cheung & Kraus 2010, Hah et al 2011. Based on ligand properties, the NR superfamily can be broadly divided into three classes: hormone, metabolic, and orphan NRs (Gadaleta & Magnani 2014). The hormone receptor subfamily includes the estrogen receptors (ERa (ESR1) and ERb (ESR2)), androgen receptor (AR), progesterone receptor (PR), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR) (Mangelsdorf et al 1995).…”