scholarly journals Cell-type specificity of short-range transcriptional repressors

2001 ◽  
Vol 98 (23) ◽  
pp. 12960-12965 ◽  
Author(s):  
J.-R. Ryu ◽  
L. K. Olson ◽  
D. N. Arnosti
NAR Cancer ◽  
2021 ◽  
Vol 3 (4) ◽  
Author(s):  
Sijie Wang ◽  
Sandra C. Ordonez-Rubiano ◽  
Alisha Dhiman ◽  
Guanming Jiao ◽  
Brayden P Strohmier ◽  
...  

Abstract Polycomb repressive complexes (PRCs) are a heterogenous collection of dozens, if not hundreds, of protein complexes composed of various combinations of subunits. PRCs are transcriptional repressors important for cell-type specificity during development, and as such, are commonly mis-regulated in cancer. PRCs are broadly characterized as PRC1 with histone ubiquitin ligase activity, or PRC2 with histone methyltransferase activity; however, the mechanism by which individual PRCs, particularly the highly diverse set of PRC1s, alter gene expression has not always been clear. Here we review the current understanding of how PRCs act, both individually and together, to establish and maintain gene repression, the biochemical contribution of individual PRC subunits, the mis-regulation of PRC function in different cancers, and the current strategies for modulating PRC activity. Increased mechanistic understanding of PRC function, as well as cancer-specific roles for individual PRC subunits, will uncover better targets and strategies for cancer therapies.


2007 ◽  
Vol 19 (8) ◽  
pp. 2624-2635 ◽  
Author(s):  
Yuko Nakagawa ◽  
Hideki Hanaoka ◽  
Masaharu Kobayashi ◽  
Kazumaru Miyoshi ◽  
Kyoko Miwa ◽  
...  

2006 ◽  
Vol 26 (22) ◽  
pp. 8515-8526 ◽  
Author(s):  
Judith Jans ◽  
George A. Garinis ◽  
Wouter Schul ◽  
Adri van Oudenaren ◽  
Michael Moorhouse ◽  
...  

ABSTRACT Cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs) comprise major UV-induced photolesions. If left unrepaired, these lesions can induce mutations and skin cancer, which is facilitated by UV-induced immunosuppression. Yet the contribution of lesion and cell type specificity to the harmful biological effects of UV exposure remains currently unclear. Using a series of photolyase-transgenic mice to ubiquitously remove either CPDs or 6-4PPs from all cells in the mouse skin or selectively from basal keratinocytes, we show that the majority of UV-induced acute effects to require the presence of CPDs in basal keratinocytes in the mouse skin. At the fundamental level of gene expression, CPDs induce the expression of genes associated with repair and recombinational processing of DNA damage, as well as apoptosis and a response to stress. At the organismal level, photolyase-mediated removal of CPDs, but not 6-4PPs, from the genome of only basal keratinocytes substantially diminishes the incidence of skin tumors; however, it does not affect the UVB-mediated immunosuppression. Taken together, these findings reveal a differential role of basal keratinocytes in these processes, providing novel insights into the skin's acute and chronic responses to UV in a lesion- and cell-type-specific manner.


2002 ◽  
Vol 76 (24) ◽  
pp. 12783-12791 ◽  
Author(s):  
Christopher R. Logg ◽  
Aki Logg ◽  
Robert J. Matusik ◽  
Bernard H. Bochner ◽  
Noriyuki Kasahara

ABSTRACT The inability of replication-defective viral vectors to efficiently transduce tumor cells in vivo has prevented the successful application of such vectors in gene therapy of cancer. To address the need for more efficient gene delivery systems, we have developed replication-competent retroviral (RCR) vectors based on murine leukemia virus (MLV). We have previously shown that such vectors are capable of transducing solid tumors in vivo with very high efficiency. While the natural requirement of MLV infection for cell division imparts a certain degree of specificity for tumor cells, additional means for confining RCR vector replication to tumor cells are desirable. Here, we investigated the parameters critical for successful tissue-specific transcriptional control of RCR vector replication by replacing various lengths of the MLV enhancer/promoter with sequences derived either from the highly prostate-specific probasin (PB) promoter or from a more potent synthetic variant of the PB promoter. We assessed the transcriptional specificity of the resulting hybrid long terminal repeats (LTRs) and the cell type specificity and efficiency of replication of vectors containing these LTRs. Incorporation of PB promoter sequences effectively restricted transcription from the LTR to prostate-derived cells and imparted prostate-specific RCR vector replication but required the stronger synthetic promoter and retention of native MLV sequences in the vicinity of the TATA box for optimal replicative efficiency and specificity. Our results have thus identified promoter strength and positioning within the LTR as important determinants for achieving both high transduction efficiency and strict cell type specificity in transcriptionally targeted RCR vectors.


Development ◽  
1971 ◽  
Vol 26 (3) ◽  
pp. 523-542
Author(s):  
K. Straznicky ◽  
R. M. Gaze ◽  
M. J. Keating

The nature of the retinotectal projection from a compound (NN or TT) eye in Xenopus raises certain problems concerning the mode of formation of connexions between the eye and the tectum. Each half of the compound eye appears to spread its connexions across the entire extent of the (apparently normal) contralateral tectum. This could indicate a certain plasticity in the way in which optic fibres can connect with the tectum. Alternatively, it is conceivable that each (similar) half of the compound eye is only able to innervate its corresponding half-tectum; in which case the uninnervated half-tectum could remain undeveloped and the innervated half-tectum could overgrow to resemble a normal tectum. This mechanism would preserve the idea of a rigidly fixed cell-to-cell specificity between retina and tectum. In an attempt to distinguish between these two mechanisms (spreading or overgrown half-tectum) we have given each of a series of Xenopus embryos at stage 32 one compound eye (NN or TT). Then, shortly after metamorphosis, we uncrossed the optic chiasma and 6 months later recorded the retinotectal projections from each eye to the tecta. Thus by connecting up the normal eye to the suspect tectum, and the compound eye to the normal tectum, we used the normal side in each case to provide an indication of the degree of abnormality with which the other side was connected. The results showed that a compound eye (NN or TT), connected to a normal tectum, gave a typical reduplicated map across the entire tectum, whereas the normal eye, when connected to the tectum which was previously innervated by the compound eye, gave an approximately normal projection across the whole of that tectum. These results lead us to conclude that, in the Xenopus visual system, no strict cell-to-cell type specificity exists; rather, what is preserved throughout these experimental manoeuvres is the polarity and extent of the projection.


1985 ◽  
Vol 5 (2) ◽  
pp. 419-421
Author(s):  
K M Zezulak ◽  
H Green

During the differentiation of preadipose 3T3 cells into adipose cells, the mRNAs for three proteins increase strikingly in abundance. To determine the degree of cell-type specificity in the expression of these mRNAs, we estimated their abundances in several nonadipose tissues of the mouse. None of these mRNAs was strictly confined to adipocytes, but the ensemble of three mRNAs was rather specific to adipocytes. Insofar as is revealed by these three markers, the distinctive phenotype of adipocytes is the result of the enhanced expression of a number of genes, none of which is completely silent in all other cell types.


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