Loss of RB compromises specific heterochromatin modifications and modulates HP1alpha dynamics.

Loss of RB compromises specific heterochromatin modifications and modulates HP1alpha dynamics. Research Abstract Details 

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Loss of RB compromises specific heterochromatin modifications and modulates HP1alpha dynamics. Abstract Text:

Hasan Siddiqui,Sejal R Fox,Ranjaka W Gunawardena,Erik S Knudsen,

Heterochromatin domains are important for gene silencing, centromere organization, and genomic stability. These genomic domains are marked with specific histone modifications, heterochromatin protein 1 (HP1) binding and DNA methylation. The retinoblastoma tumor suppressor, RB mediates transcriptional repression and functionally interacts with a number of factors that are involved in heterochromatin biology including HP1, Suv39h1, DNMT1, and components of the SWI/SNF chromatin remodeling complex. To analyze the specific influence of RB loss on chromatin modification, mouse adult fibroblasts (MAFs) derived from Rb(loxP/loxP) mice were utilized to acutely knockout RB. In this setting, target genes of RB are deregulated. Additionally, changes in histone modifications were observed. Specifically, histone H4 lysine 20 trimethylation was absent from heterochromatin domains following loss of RB and there were changes in the relative levels of histone modifications between RB-proficient and deficient cells. While RB loss significantly altered the modifications associated with heterochromatin domains, these domains were readily identified and efficiently mediated the recruitment of HP1alpha. Kinetic analyses of HP1alpha within the heterochromatin domains present in RB-deficient cells indicated that loss of RB retarded HP1alpha dynamics, indicating that HP1alpha is paradoxically more tightly associated with heterochromatin in the absence of RB function. Combined, these analyses demonstrate that loss of RB has global effects on chromatin modifications and dynamics.

Loss of RB compromises specific heterochromatin modifications and modulates HP1alpha dynamics. Publishing Authors By Initials

H Siddiqui,SR Fox,RW Gunawardena,ES Knudsen,

For similar proteins: dna-binding proteins: retinoblastoma protein research abstracts see: proteins: dna-binding proteins: retinoblastoma protein research

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Loss of RB compromises specific heterochromatin modifications and modulates HP1alpha dynamics. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of cellular physiology

VOLUME: 211

Page Numbers: 131-7

Journal Abbreviation: J. Cell. Physiol.

ISSN: 0021-9541

DAY: 3

MONTH: Apr

YEAR: 2007

Loss of RB compromises specific heterochromatin modifications and modulates HP1alpha dynamics. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 50222

Loss of RB compromises specific heterochromatin modifications and modulates HP1alpha dynamics. Keywords Mesh Terms:

KEYWORDS: Retinoblastoma Protein

MESH TERMS: metabolism

Chemical & Substance for Abstract: Loss of RB compromises specific heterochromatin modifications and modulates HP1alpha dynamics. Information

Substance Name: heterochromatin-specific nonhistone chro

Registry Number: 107283-02-3

Grant and Affiliation Information for Loss of RB compromises specific heterochromatin modifications and modulates HP1alpha dynamics.

AFFILIATION: Department of Cell Biology, Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0521, USA. siddiqhn@email.uc.edu

Country: United States

AGENCY: United States NCI

GRANT: CA 104213-02

ACRONYM: CA

MEDLINETA: J Cell Physiol

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