Project description:In breast cancer cells, some topologically associating domains (TADs) behave as hormonal gene regulation units, within which genes transcription is coordinately regulated in response to steroid hormones. Here we further described that responsive TADs contain 20-100 kb-long clusters of intermingled estrogen receptor (ER) and progesterone receptor (PR) binding sites, hereafter called Hormone-Control Regions (HCRs). In T47D cells, we identified more than 200 HCRs, which are frequently bound by unliganded ER and PR. These HCRs establish steady long-distance inter-TAD interactions between them and organize characteristic looping structures with promoters even in the absence of hormones in ER+-PR+ cells. This organization is dependent on the expression of the receptors and is further dynamically modulated in response to steroid hormones. HCRs function as platforms integrating different signals resulting in some cases in opposite transcriptional responses to estrogens or progestins. Altogether, these results suggest that steroid hormone receptors act not only as hormone-regulated sequence-specific transcription factors, but also as local and global genome organizers.

2018-11-16 | GSE109229 | GEO

Regulation of insect steroid hormone biosynthesis by innervating peptidergic neurons.

Project description: Not available

| S-EPMC1482630 | biostudies-literature

A specialized Hsp90 co-chaperone network regulates steroid hormone receptor response to ligand

Project description:Heat shock protein-90 chaperone machinery is involved in the stability and activity of its client proteins. The chaperone function of Hsp90 is regulated by co-chaperones and post-translational modifications. Although structural evidence exists for Hsp90 interaction with clients, our understanding of the impact of Hsp90 chaperone function towards client activity in cells remains elusive. Here, we dissected the impact of newly identified co-chaperones in higher eukaryotes, FNIP1/2 (FNIPs) and Tsc1, towards Hsp90 client activity. Our data show that Tsc1 and FNIP2 form mutually exclusive complexes with FNIP1 and that unlike Tsc1, FNIP1/2 interact with the catalytic residue of Hsp90. Functionally, these co-chaperone complexes increase the affinity of the steroid hormone receptors glucocorticoid receptor and estrogen receptor to their ligands in vivo. Here, we provide a model for the responsiveness of the steroid hormone receptor activation upon ligand binding as a consequence of their association with specific Hsp90:co-chaperone subpopulations.

2023-05-30 | PXD030486 | Pride

Hormone Control Regions mediate steroid receptor-dependent genome organizations

Project description:Hormone Control Regions mediate steroid receptor-dependent genome organizations

| PRJNA430222 | ENA

GLIS3 is indispensable for TSH/TSHR-dependent thyroid hormone biosynthesis and follicular cell proliferation

Project description:Deficiency in Krüppel-like zinc finger transcription factor, GLI-Similar 3 (GLIS3) in humans is associated with the development of congenital hypothyroidism. However, the functions of GLIS3 in the thyroid gland and by what mechanism GLIS3-dysfunction causes hypothyroidism are unknown. In this study, we demonstrate that GLIS3 acts downstream of thyroid stimulating hormone (TSH)/TSHR and is indispensable for TSH/TSHR-mediated induction of thyroid follicular cell proliferation and thyroid hormone biosynthesis. ChIP-Seq and promoter analysis revealed that GLIS3 is critical for the transcriptional activation of several genes required for thyroid hormone biosynthesis, including the iodide transporters Nis and Pds, indicating that these genes are directly regulated by GLIS3. The repression of cell proliferation regulatory genes is due to the inhibition of TSH-mediated activation of the mTORC1/RPS6 pathway as well as direct transcriptional regulation of several cell division-related genes by GLIS3. Consequently, GLIS3-deficiency prevents the development of goiter as well as the induction of inflammatory and fibrotic genes during chronic elevation of circulating TSH. Our study identifies GLIS3 as a new and key regulator of TSH/TSHR-mediated thyroid hormone biosynthesis and proliferation of thyroid follicular cells, and uncovers a mechanism by which GLIS3-deficiency causes congenital hypothyroidism and prevents goiter development.

2017-08-30 | GSE103297 | GEO

Genome-wide transcriptional analysis of PTTH-stimulated Bombyx prothoracic gland

Project description:This is part of a cross-species approach to characterize transcriptional response of the insect prothoracic gland (PG) to the prothoracicotropic hormone (PTTH). Genome-wide response of the PG to PTTH was analyzed in vitro in Bombyx and in vivo in Drosophila, and the results were compared to identify common components in the PTTH signaling pathway. Bombyx PGs were incubated in vitro for 1 or 3 hours with or without 10 nM recombinant PTTH. 12-18 larvae were used to prepare each RNA sample, and the experiment was conducted twice. Total RNA samples from two independent preparations were combined to obtain a single RNA sample for each treatment, which was subjected to RNA-seq.

2016-07-29 | E-GEOD-84963 | biostudies-arrayexpress

Interdependent nutrient availability and steroid hormone signals facilitate root growth plasticity

Project description:Interdependent nutrient availability and steroid hormone signals facilitate root growth plasticity

| PRJNA470669 | ENA