Cell proliferation and differentiation are coordinated by synchronized patterns of gene expression. The regulation of these patterns is achieved, in part, through epigenetic mechanisms that affect the nature of DNA packaging into chromatin. Specifically, post-translational modifications to histone tails impact the structural dynamics of nucleosomes, thereby affecting DNA accessibility to transcriptional complexes. Accumulating evidence suggests that transcriptional regulators facilitate these alterations, resulting in altered local gene transcription. Thus, the structural interpretations of histone modifications are responsible for the establishment and maintenance of discrete programs of gene expression that ultimately correspond with distinct biological outcomes. Most histone lysine methyltransferases catalyze methyl transfer by way of the SET domain, a module encoded within many proteins that regulate diverse processes, including some critical for development and proper progression of the cell cycle. One such group of proteins, the SET and MYND domain (Smyd) family have been demonstrated to be direct regulators of tumorigenesis and essential developmental processes. Presented here is a functional characterization of two members of that family, Smyd2 and Smyd3. Smyd2 is identified as a member of the Smyd family and reported here to possess SET-dependent histone H3, lysine 36-specific methyltransferase activity. Smyd2 specifically associates with the Sin3A histone deacetylase complex, suggesting a link between two independent chromatin modification activities. Finally, over-expression of Smyd2 in fibroblasts is shown to significantly suppress their rate of growth. It is therefore proposed that Smyd2-mediated chromatin modifications regulate specific gene expression, thereby having important implications for normal and neoplastic cell proliferation. Aberrant expression of the histone H3-lysine 4-specific methyltransferase, Smyd3, has been implicated in colorectal, hepatocellular, and breast cell carcinogenesis. Here, Smyd3 is also shown to target histone H4, lysine 20 (H4K20). However, over-expression of Smyd3 in fibroblasts results in global reduction of trimethylation at H4K20 and this is accompanied by a striking increase in cell proliferation. As the methylation of H3K4 and H4K20 are normally associated with conflicting biological functions, I predict that these differential activities of Smyd3 are manifest under spatially and/or temporally distinct conditions, in the presence of different associating complexes, thereby resulting in effects that may be antagonistic of one another. / text

No description available.

No description available.

Epithelial-mesenchymal interactions are central to the development of skin and skin appendages in vertebrates. These interactions continue throughout adult life and underpin the cyclic growth and loss of hair in mammals. While the molecular basis of such interactions are being gradually uncovered, at the cellular level many questions remain unanswered. For example, the localisation and role of hair follicle epithelial stem cells remains a subject of debate, as does the function of the dermal sheath component. In embryonic appendage development there is strong evidence for common signalling mechanisms, but the degree to which epithelial-mesenchymal communication diverges in different adult appendages remains as yet undiscovered. I have studied the replicative abilities of germinative epidermal (GE) cells of the rat vibrissa follicle by single and repeated plucking of fibres from individual follicles. In both cases, the cellular events following fibre removal were scrutinised at intervals up to 9 days using histology, and cell proliferation and cell death markers. Follicles that were repeatedly plucked had their growing hairs measured at regular intervals. By analysing cell proliferation patterns I found that the new regenerated epidermal matrix came from residual GE cells left in the follicle base - after both single and repeated depilations. Indeed plucking appeared to cause an initial inhibition of proliferative activity in the follicle upper outer root sheath, the other candidate region for supplying a new matrix. Length measurements of the regenerated hairs demonstrated that the repeatedly plucked follicles produced total cumulative lengths of fibre between 60 and 265% longer than expected, as determined by measuring the original club fibre lengths. In vivo amputation of plucked follicles demonstrated that the residual GE cells have the ability to regenerate a new matrix and new fibre without any contribution from cells from the upper region of the follicle. These studies, along with in vitro observations of prolonged replicative abilities of bulb cells suggest that the GE cells have a proliferative capacity which is beyond that of one cycle. This raises the possibility that GE cells are not transient amplifying cells with limited proliferative potential and strongly suggests that the duration of anagen cannot be attributed to the replicative limitations of the GE cells. The behaviour and interactive abilities of dermal cells isolated from three different skin appendages (rat vibrissa follicle, rat claw unit, and pigeon feather follicle) were characterised by cell culture, immunohistochemistry and dermal-epidermal recombinations. Dermal cells from all the above appendages demonstrated common aggregation properties in culture and all expressed a-smooth muscle actin. When recombined with epidermal cells and implanted onto host rats, dermal sheath cells from the lower part of vibrissa follicles produced a robust skin-like structure with a normal

Thesis (M.S.) -- Central Connecticut State University, 2008. / Thesis advisor: Ruth Rollin. "... in partial fulfillment of the requirements for the degree of Master of Science in Biological Sciences." Includes bibliographical references (leaves 37-45). Also available via the World Wide Web.

Thesis (M.S.)--Worcester Polytechnic Institute. / Keywords: MCF-7; genistein; breast cancer; PCNA; phytoestrogens. Includes bibliographical references (p. 37-41).

Thesis (Ph. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.

No description available.

A study has been made of the effect of cell population density and virus-transformation on the transport of K+, inorganic phosphate (Pi) and 2-deoxyglucose in cultured mouse fibroblasts. Normal, untransformed 3T3 show a marked reduction (3-5 fold) in the influx of K+, Pi and 2-deoxyglucose with increasing; cell population density. The reduce-in transport begins at low cell densities and procedes the cessation of cell growth. In contrast, virus-transformed 3T3 cells do not exhibit similar density-dependent reductions in transport. In these cells the influx of K+ and 2-deoxyglucos is independent of cell density. The influx of Pi does decrease with increasing cell density but to a lesser extent and at much higher population densities than in cells. At low cell densities the influx of Pi and 2-deoxglucose in 3T3 cells is only slightly lower than the influx into transformed cells. For K+ the influx in 3T3 cells is slightly higher than in the transformed cells. At higher cell densities the transformed cells exhibit the higher rates of uptake of all three substrates due to the density-dependent transport reduction in the 3T3 cells. Virus-transformation per se does not, therefore, lead to any great increase in transport capacity. In all cases the density-dependent transport reductions are attributable to a decreased Vmax with no change in the Km of the system. The transport sites of normal and virus-transformed cells appear to be qualitatively similar since no significant differences were found for transport Km's between the cell lines. The density-dependent reduction of the K+ influx in 3T3 cells is due to a decrease in "Na-pump" activity with no change in the passive permeability of the cell membrane to K. This reduced "Na-pump" activity is accompanied by a decrease in [K+]i and an increase in [Na+]i. The [K+]i and [Na+]i of virus-transformed cells are not markedly affected by change in cell density. The [K+]i of transformed cells is slightly higher than the [K+]i of untransformed cells at low cell density and almost 2-fold greater than the [K+]i of high density untransformed cells. The cardiac glycoside, ouabain, inhibits Na-K exchange in both untransformed and transformed cells. In the transformed cells the drug also produces a secondary effect ie. a stimulation of K-K exchange. Evidence is presented which suggests that this difference is related known changes in the lipid properties of virus-transformed cell membranes. The inward transport of Pi occurs predominantly via a carrier-mediated, Na-dependent process. A small Na-independent influx of Pi is also present. Preliminary evidence suggests that the outward movement of Pi is also Na-dependent. A model for Na-coupled Pi transport is presented and discussed briefly. The density-dependent reduction of Pi transport in 3T3 cells is due to a decreased Na-dependent influx with no change in the Na-independent component. The addition of fresh complete medium to quiescent 3T3 cells causes a rapid increase in the influx of Pi and 2-deoxyglucose. Fresh medium without scrum does not increase transport. For bott substrates the increased transport results from a higher Vmax with no alteration in Km. Under normal culture conditions this scrum-stimulation of transport is independent of protein synthesis. However, an additional increase in Pi transport occurs when fresh complete medium is added to serum-starved 3T3 cells. This second increase is inhibited by cyclohoximide indicating a requirement for protein synthesis. A model is presented which attempts to explain the effects of serum growth factors in terms of their action on transport systems.