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You searched for subject:(HOMEDOMAIN PROTEIN). Showing records 1 – 2 of 2 total matches.

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Temple University

1. Singh, Maneet. TRANSCRIPTIONAL REGULATION OF OSTEOACTIVIN EXPRESSION BY BMP-2 IN OSTEOBLASTS.

Degree: PhD, 2011, Temple University

Cell Biology

Osteoactivin (OA) is a glycoprotein required for the differentiation of osteoblasts. In osteoblasts, Bone Morphogenetic Protein-2 (BMP-2) activated Smad1 signaling enhances OA expression. However, the transcriptional regulation of OA gene expression by BMP-2 is still unknown. The aim of this study was to characterize BMP-2-induced transcription factors that regulate OA gene expression during osteoblast differentiation. The stimulatory effects of BMP-2 on OA transcription were established by cloning the proximal 0.96kb of rat OA promoter region in a luciferase reporter vector in various osteogenic cell types. Further, by deletion and mutagenesis analyses of the cloned OA promoter, key binding sites for osteogenic transcription factors namely, Runx2, Smad1, Smad4 and homeodomain proteins (Dlx3, Dlx5 and Msx2) were identified and characterized. Utilizing specific siRNAs to knock down Runx2, Smad1, Smad4, Dlx3, Dlx5 or Msx2 proteins in osteoblasts, we found that Runx2, Smad1, Smad4, Dlx3 and Dlx5 proteins up-regulate OA transcription, whereas, Msx2 down-regulated OA gene expression. These specific effects of transcription factors on OA promoter regulation were confirmed by forced expression of transcription factors. Most notably, BMP-2-stimulated cooperative and synergistic interactions between Runx2-Smad1 proteins and Dlx3-Dlx5 proteins that up-regulate OA promoter activity. Electrophoretic mobility shift and supershift assays demonstrated that BMP-2 stimulates interactions between Runx2, Smad1 and Smad4 and homeodomain transcription factors with the OA promoter regions flanking the -585 Runx2 binding site, the -248 Smad binding site and the region between the -852 and the -843 homeodomain binding sites relative to transcription start site. The OA promoter region was occupied by Runx2 and also Dlx3 transcription factors during proliferation stages of osteoblast differentiation. As the osteoblasts progress from proliferation to matrix maturation stages of differentiation, the OA promoter was predominantly occupied by Runx2 and to a lesser extent Dlx5 in response to BMP-2. Finally, during matrix mineralization stages of osteoblast differentiation, BMP-2-induced a robust recruitment of Dlx5, Smad1, Dlx3 and Msx2 proteins with simultaneous dissociation of Runx2 from the OA promoter region. In conclusion, the BMP-2-induced osteogenic transcription factors Runx2, Smad1, Smad4, Dlx3, Dlx5 and Msx2 provide key molecular switches that regulate OA transcription during osteoblast differentiation.

Temple University – Theses

Advisors/Committee Members: Safadi, Fayez F., Popoff, Steven N., Barbe, Mary F., Sanjay, Archana, Monroy, Alexandra M., Owen, Thomas A..

Subjects/Keywords: Cellular Biology; Molecular Biology; Biology; HOMEDOMAIN PROTEIN; OSTEOACTIVIN; OSTEOBLAST DIFFERENTIATION; RUNX2; SMAD1 AND SMAD4; TRANSCRIPTIONAL REGULATION

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Singh, M. (2011). TRANSCRIPTIONAL REGULATION OF OSTEOACTIVIN EXPRESSION BY BMP-2 IN OSTEOBLASTS. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,135232

Chicago Manual of Style (16th Edition):

Singh, Maneet. “TRANSCRIPTIONAL REGULATION OF OSTEOACTIVIN EXPRESSION BY BMP-2 IN OSTEOBLASTS.” 2011. Doctoral Dissertation, Temple University. Accessed October 25, 2020. http://digital.library.temple.edu/u?/p245801coll10,135232.

MLA Handbook (7th Edition):

Singh, Maneet. “TRANSCRIPTIONAL REGULATION OF OSTEOACTIVIN EXPRESSION BY BMP-2 IN OSTEOBLASTS.” 2011. Web. 25 Oct 2020.

Vancouver:

Singh M. TRANSCRIPTIONAL REGULATION OF OSTEOACTIVIN EXPRESSION BY BMP-2 IN OSTEOBLASTS. [Internet] [Doctoral dissertation]. Temple University; 2011. [cited 2020 Oct 25]. Available from: http://digital.library.temple.edu/u?/p245801coll10,135232.

Council of Science Editors:

Singh M. TRANSCRIPTIONAL REGULATION OF OSTEOACTIVIN EXPRESSION BY BMP-2 IN OSTEOBLASTS. [Doctoral Dissertation]. Temple University; 2011. Available from: http://digital.library.temple.edu/u?/p245801coll10,135232


UCLA

2. Liu, Ao. On Transcriptional Regulation by TOPLESS in Arabidopsis thaliana.

Degree: Molec, Cell, & Dev Biology, 2018, UCLA

How multicellular organisms modulate transcription in response to internal and external cues is a fundamental question in plant and animal development and growth. In Arabidopsis, TOPLESS(TPL), a Groucho/Tup1 like co-repressor, is involved in the transcriptional response to multiple plant hormones and plays a crucial role in a range of major developmental processes, such as embryonic apical-basal patterning and post-embryonic floral patterning. This dissertation describes the advances made toward the elucidation of the molecular mechanisms underlying transcriptional regulation by TPL. As a co-repressor, TPL lacks intrinsic DNA binding activity and has been shown to be recruited by transcription factors with repressive motifs. To date, a range of transcription factors have been reported to interact with TPL, yet the functionality of most of these interactions is not known. We found that the members of the Class III Homedomain-Leucine Zipper (HD- ZIPIII) transcription factor family co-localize with TPL to form complexes at the promoters of thousands of genes in the genome. HD-ZIPIIIs both antagonistically and cooperatively regulate entire pathways at multiple steps in a cell or tissue specific manner. The five members in the family form homo- and hetero-dimers and act both as activators and repressors. The association with TPL confers the repressive function of HD-ZIPIIIs. Just like its counterparts in animals and fungi, TPL also associates with histone deacetylases(HDACs) to repress transcription. We characterized the binding profiles of TPL and HDA19, a class I histone deacetylase that interacts with TPL, and found they tend to bind to the promoters of dynamically expressed genes. Almost all HDA19 peaks have an overlapping TPL peak, while about half of the TPL peaks are in common with HDA19, suggesting HDA19 is involved only at a subset of TPL targets. Specifically, we found the three members of the evolutionarily conserved NAM/CUC (for NO APICAL MERISTEM and CUP-SHAPED COTYLEDON) transcription factors, CUC1, CUC2 and CUC3, are regulated by TPL and HDA19 to control boundary specification during floral development. Finally, we showed that TPL interacts with lysine 27-trimethylated histone H3(H3K27me3) and binds to a significant number of genomic regions with this modification, suggesting a novel layer of regulation which has not been reported in animals. A decrease in TPL binding was observed in plants that have a mutation in the Polycomb Repressive Complexes 2 (PRC2), which mediates the deposition of H3K27me3. TPL itself affects H3K27me3 levels and interacts with a component of the PRC1 complex, which recognizes H3K27me3 and further contributes to chromatin compaction. Genes potentially regulated by both TPL and PRCs are involved in multiple developmental processes and stress responses. These data suggest that upon the recruitment of TPL, binding affinity is enhanced by H3K27me3 marked nucleosomes and TPL may further contributes to the repressive transcriptional state via the association with Polycomb group (PcG)…

Subjects/Keywords: Molecular biology; Developmental biology; Class III Homedomain-Leucine Zipper; H3K27me3; histone deacetylase; Polycomb group protein; TOPLESS; transcriptional regulation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Liu, A. (2018). On Transcriptional Regulation by TOPLESS in Arabidopsis thaliana. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/41g4265p

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Liu, Ao. “On Transcriptional Regulation by TOPLESS in Arabidopsis thaliana.” 2018. Thesis, UCLA. Accessed October 25, 2020. http://www.escholarship.org/uc/item/41g4265p.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Liu, Ao. “On Transcriptional Regulation by TOPLESS in Arabidopsis thaliana.” 2018. Web. 25 Oct 2020.

Vancouver:

Liu A. On Transcriptional Regulation by TOPLESS in Arabidopsis thaliana. [Internet] [Thesis]. UCLA; 2018. [cited 2020 Oct 25]. Available from: http://www.escholarship.org/uc/item/41g4265p.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Liu A. On Transcriptional Regulation by TOPLESS in Arabidopsis thaliana. [Thesis]. UCLA; 2018. Available from: http://www.escholarship.org/uc/item/41g4265p

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.