scholarly journals Mechanism of Histone H1-Stimulated Glucocorticoid Receptor DNA Binding In Vivo

2007 ◽  
Vol 27 (6) ◽  
pp. 2398-2410 ◽  
Author(s):  
Sergey Belikov ◽  
Carolina Åstrand ◽  
Örjan Wrange
Keyword(s):  
Dna Binding ◽  
Glucocorticoid Receptor ◽  
Histone H1 ◽  
Micrococcal Nuclease ◽  
Chromatin Domain ◽  
Asymmetric Distribution ◽  
Mouse Mammary Tumor ◽  
Glucocorticoid Response ◽  
Tumor Virus

ABSTRACT Xenopus oocytes lack somatic linker histone H1 but contain an oocyte-specific variant, B4. The glucocorticoid receptor (GR) inducible mouse mammary tumor virus (MMTV) promoter was reconstituted in Xenopus oocytes to address the effects of histone H1. The expression of Xenopus H1A (H1) via cytoplasmic mRNA injection resulted in H1 incorporation into in vivo assembled chromatin based on (i) the appearance of a chromatosome stop, (ii) the increased nucleosome repeat length (NRL), and (iii) H1-DNA binding assayed by chromatin immunoprecipitation (ChIP). The H1 effect on the NRL was saturable and hence represents H1-binding to a specific site. A subsaturating level of H1 enhanced the hormone-dependent binding of GR to the glucocorticoid response elements (GREs) and the hormone-dependent MMTV transcription while it reduced the access to DNA as revealed by micrococcal nuclease (MNase) analysis. These H1 effects were lost at higher levels of H1. ChIP and MNase analysis revealed a hormone-dependent dissociation of H1 from the activated chromatin domain. The proposed mechanism of H1-induced GR binding is based on two effects: (i) a GR-induced asymmetric distribution of H1 in favor of inactive chromatin and (ii) an H1-induced reduction in DNA access. These effects results in increased concentration of free GR and, hence, in increased GR-GRE binding.

scholarly journals Mechanism of Histone H1-Stimulated Glucocorticoid Receptor DNA Binding In Vivo

2008 ◽  
Vol 28 (21) ◽  
pp. 6730-6730
Author(s):  
Sergey Belikov ◽  
Carolina Åstrand ◽  
Örjan Wrange
Keyword(s):  
Dna Binding ◽  
Glucocorticoid Receptor ◽  
Histone H1

scholarly journals Histone H1 Phosphorylation by Cdk2 Selectively Modulates Mouse Mammary Tumor Virus Transcription through Chromatin Remodeling

2001 ◽  
Vol 21 (16) ◽  
pp. 5417-5425 ◽  
Author(s):  
Rabindra N. Bhattacharjee ◽  
Geoffrey C. Banks ◽  
Kevin W. Trotter ◽  
Huay-Leng Lee ◽  
Trevor K. Archer
Keyword(s):  
Chromatin Remodeling ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Histone H1 ◽  
Necessary Condition ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Mmtv Promoter

ABSTRACT Transcriptional activation of the mouse mammary tumor virus (MMTV) promoter by ligand-bound glucocorticoid receptor (GR) is transient. Previously, we demonstrated that prolonged hormone exposure results in displacement of the transcription factor nuclear factor 1 (NF1) and the basal transcription complex from the promoter, the dephosphorylation of histone H1, and the establishment of a repressive chromatin structure. We have explored the mechanistic link between histone H1 dephosphorylation and silencing of the MMTV promoter by describing the putative kinase responsible for H1 phosphorylation. Both in vitro kinase assays and in vivo protein expression studies suggest that in hormone-treated cells the ability of cdk2 to phosphorylate histone H1 is decreased and the cdk2 inhibitory p21 protein level is increased. To address the role of cdk2 and histone H1 dephosphorylation in the silencing of the MMTV promoter, we used potent cdk2 inhibitors, Roscovitine and CVT-313, to generate an MMTV promoter which is associated predominantly with the dephosphorylated form of histone H1. Both Roscovitine and CVT-313 block phosphorylation of histone H1 and, under these conditions, the GR is unable to remodel chromatin, recruit transcription factors to the promoter, or stimulate MMTV mRNA accumulation. These results suggest a model where cdk2-directed histone H1 phosphorylation is a necessary condition to permit GR-mediated chromatin remodeling and activation of the MMTV promoter in vivo.

scholarly journals The HSA Domain of BRG1 Mediates Critical Interactions Required for Glucocorticoid Receptor-Dependent Transcriptional Activation In Vivo

2007 ◽  
Vol 28 (4) ◽  
pp. 1413-1426 ◽  
Author(s):  
Kevin W. Trotter ◽  
Hua-Ying Fan ◽  
Melissa L. Ivey ◽  
Robert E. Kingston ◽  
Trevor K. Archer
Keyword(s):  
Glucocorticoid Receptor ◽  
Chromatin Remodeling ◽  
Protein Interactions ◽  
Transcriptional Activation ◽  
Critical Factor ◽  
Receptor Complexes ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Eukaryotic Dna

ABSTRACT The packaging of eukaryotic DNA into chromatin can create an impediment to transcription by hindering binding of essential factors required for transcription. The mammalian SWI/SNF remodeling complex has been shown to alter local chromatin structure and facilitate recruitment of transcription factors. BRG1 (or hBrm), the central ATPase of the human SWI/SNF complex, is a critical factor for the functional activity of nuclear receptor complexes. Analysis using BRG1/SNF2h chimeras suggests BRG1 may contain previously uncharacterized functional motifs important for SWI/SNF. To identify these regions, BRG1 truncation and deletion mutants were designed, characterized, and utilized in a series of assays to evaluate transcriptional activation and chromatin remodeling by the glucocorticoid receptor. We identified a domain within the N terminus of BRG1 that mediates critical protein interactions within SWI/SNF. We find the HSA domain of BRG1 is required to mediate the interaction with BAF250a/ARID1A and show this association is necessary for transcriptional activation from chromatin mouse mammary tumor virus or endogenous promoters in vivo. These studies suggest BAF250a is a necessary facilitator of BRG1-mediated chromatin remodeling required for SWI/SNF-dependent transcriptional activation.

scholarly journals Heregulin Co-opts PR Transcriptional Action Via Stat3 Role As a Coregulator to Drive Cancer Growth

2015 ◽  
Vol 29 (10) ◽  
pp. 1468-1485 ◽  
Author(s):  
Cecilia J. Proietti ◽  
Franco Izzo ◽  
María Celeste Díaz Flaqué ◽  
Rosalía Cordo Russo ◽  
Leandro Venturutti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Cancer Growth ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Virus Promoter

Abstract Accumulated findings have demonstrated the presence of bidirectional interactions between progesterone receptor (PR) and the ErbB family of receptor tyrosine kinases signaling pathways in breast cancer. We previously revealed signal transducer and activator of transcription 3 (Stat3) as a nodal convergence point between said signaling pathways proving that Stat3 is activated by one of the ErbBs' ligands, heregulin (HRG)β1 via ErbB2 and through the co-option of PR as a signaling molecule. Here, we found that HRGβ1 induced Stat3 recruitment to the promoters of the progestin-regulated cell cycle modulators Bcl-XL and p21CIP1 and also stimulated Stat3 binding to the mouse mammary tumor virus promoter, which carries consensus progesterone response elements. Interestingly, HRGβ1-activated Stat3 displayed differential functions on PR activity depending on the promoter bound. Indeed, Stat3 was required for PR binding in bcl-X, p21CIP1, and c-myc promoters while exerting a PR coactivator function on the mouse mammary tumor virus promoter. Stat3 also proved to be necessary for HRGβ1-induced in vivo tumor growth. Our results endow Stat3 a novel function as a coregulator of HRGβ1-activated PR to promote breast cancer growth. These findings underscore the importance of understanding the complex interactions between PR and other regulatory factors, such as Stat3, that contribute to determine the context-dependent transcriptional actions of PR.

scholarly journals The DNA-binding protein HTa from Thermoplasma acidophilum is an archaeal histone analog

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Antoine Hocher ◽  
Maria Rojec ◽  
Jacob B Swadling ◽  
Alexander Esin ◽  
Tobias Warnecke
Keyword(s):  
Dna Binding ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
Coli Strain ◽  
Micrococcal Nuclease ◽  
Thermoplasma Acidophilum ◽  
Chromatin Architecture ◽  
Archaeal Histone

Histones are a principal constituent of chromatin in eukaryotes and fundamental to our understanding of eukaryotic gene regulation. In archaea, histones are widespread but not universal: several lineages have lost histone genes. What prompted or facilitated these losses and how archaea without histones organize their chromatin remains largely unknown. Here, we elucidate primary chromatin architecture in an archaeon without histones, Thermoplasma acidophilum, which harbors a HU family protein (HTa) that protects part of the genome from micrococcal nuclease digestion. Charting HTa-based chromatin architecture in vitro, in vivo and in an HTa-expressing E. coli strain, we present evidence that HTa is an archaeal histone analog. HTa preferentially binds to GC-rich sequences, exhibits invariant positioning throughout the growth cycle, and shows archaeal histone-like oligomerization behavior. Our results suggest that HTa, a DNA-binding protein of bacterial origin, has converged onto an architectural role filled by histones in other archaea.

Two regions of the mouse mammary tumor virus long terminal repeat regulate the activity of its promoter in mammary cell lines

1991 ◽  
Vol 11 (5) ◽  
pp. 2529-2537 ◽  
Author(s):  
P Lefebvre ◽  
D S Berard ◽  
M G Cordingley ◽  
G L Hager
Keyword(s):  
Long Terminal Repeat ◽  
Cell Lines ◽  
Mouse Mammary Tumor Virus ◽  
Terminal Repeat ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Mammary Cell ◽  
Tumor Virus ◽  
Mmtv Promoter

In vivo expression of the mouse mammary tumor virus (MMTV) is restricted to a few organs, with the highest rate of transcription found in the mammary gland. Using a series of mammary and nonmammary murine cell lines, we have identified two regulatory elements, located upstream of the hormone responsive element, that specifically regulate the MMTV promoter. The first element displays an enhancerlike activity and is coincident with the binding of a nuclear factor (designated MP4; position -1078 to -1052 in the long terminal repeat) whose presence is apparently restricted to mammary cell lines. The second regulatory region mediates a repressive activity and is mapped to the long terminal repeat segment from -415 to -483. This repression is specific for a particular subtype of mammary cells (RAC cells) able to grow under two differentiation states (A. Sonnenberg, H. Daams, J. Calafat, and J. Hilgers, Cancer Res. 46:5913-5922, 1986). The MMTV promoter in mammary cell lines thus appears to be modulated by two cis-acting elements that are likely to be involved in tissue-specific expression in vivo.

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