RB-MEDIATED REGULATION OF TRANSCRIPTION AND EPIGENETIC MODIFICATIONS

RB-MEDIATED REGULATION OF TRANSCRIPTION AND EPIGENETIC MODIFICATIONS

Bibliographic Details
Main Author: SIDDIQUI, HASAN
Language:English
Published: University of Cincinnati / OhioLINK 2006
Subjects:
Cancer
Cell Cycle
Retinoblastoma tumor suppressor
Chromatin modifications
Transcription
SWI/SNF
HDAC
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1148053497
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin11480534972021-08-03T06:11:11Z RB-MEDIATED REGULATION OF TRANSCRIPTION AND EPIGENETIC MODIFICATIONS SIDDIQUI, HASAN Cancer Cell Cycle Retinoblastoma tumor suppressor Chromatin modifications Transcription SWI/SNF HDAC The retinoblastoma tumor suppressor protein (RB) is the ‘master regulator’ of cellular proliferation and is targeted for inactivation in the majority of human tumors. RB inhibits proliferation by repressing the transcription of genes essential for cell cycle progression. Although RB interacts with numerous chromatin modifying (e.g., histone deacetylases or HDACs, histone methyltransferases or HMTases) and remodeling (e.g., SWI/SNF chromatin remodeling complex) enzymes, the functional significance of these interactions is not apparent. Here we investigated the role of chromatin modifying and remodeling enzymes in RB-mediated transcriptional repression and epigenetic modifications. We find that active RB mediates histone deacetylation on endogenous RB target gene promoters. We also demonstrate that this deacetylation is HDAC dependent, since the HDAC inhibitor trichostatin A (TSA) prevented histone deacetylation at each promoter. However, TSA treatment blocked RB repression of only a specific subset of genes, demonstrating that the requirement of HDACs for RB-mediated transcriptional repression is promoter specific. Furthermore, we find that cell cycle inhibitory action of RB is not intrinsically dependent on the ability to recruit HDAC activity. The HDAC-independent repression was not associated with DNA methylation or gene silencing since it was readily reversible. We show that this form of repression resulted in altered chromatin structure and was dependent on SWI/SNF chromatin remodeling activity. Importantly, we demonstrate that SWI/SNF is required for histone deacetylation of RB target promoters. Furthermore, we show that loss of RB disrupts a specific epigenetic modification and heterochromatin protein 1 (HP1) dynamics in the chromatin. These studies highlight the influence of RB on transcriptional repression and epigenetic modifications. 2006-07-13 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1148053497 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1148053497 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Cancer
Cell Cycle
Retinoblastoma tumor suppressor
Chromatin modifications
Transcription
SWI/SNF
HDAC
spellingShingle Cancer
Cell Cycle
Retinoblastoma tumor suppressor
Chromatin modifications
Transcription
SWI/SNF
HDAC
SIDDIQUI, HASAN
RB-MEDIATED REGULATION OF TRANSCRIPTION AND EPIGENETIC MODIFICATIONS
author SIDDIQUI, HASAN
author_facet SIDDIQUI, HASAN
author_sort SIDDIQUI, HASAN
title RB-MEDIATED REGULATION OF TRANSCRIPTION AND EPIGENETIC MODIFICATIONS
title_short RB-MEDIATED REGULATION OF TRANSCRIPTION AND EPIGENETIC MODIFICATIONS
title_full RB-MEDIATED REGULATION OF TRANSCRIPTION AND EPIGENETIC MODIFICATIONS
title_fullStr RB-MEDIATED REGULATION OF TRANSCRIPTION AND EPIGENETIC MODIFICATIONS
title_full_unstemmed RB-MEDIATED REGULATION OF TRANSCRIPTION AND EPIGENETIC MODIFICATIONS
title_sort rb-mediated regulation of transcription and epigenetic modifications
publisher University of Cincinnati / OhioLINK
publishDate 2006
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1148053497
work_keys_str_mv AT siddiquihasan rbmediatedregulationoftranscriptionandepigeneticmodifications
_version_ 1719432346817527808

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