Dataset Information

CENP-B cooperates with Set1 in bidirectional transcriptional silencing and genome organization of retrotransposons.

ABSTRACT: Regulation of transposable elements (TEs) is critical to the integrity of the host genome. The fission yeast Schizosaccharomyces pombe homologs of mammalian CENP-B perform a host genome surveillance role by controlling Tf2 long terminal repeat (LTR) retrotransposons. However, the mechanisms by which CENP-Bs effect their functions are ill defined. Here, we show that the multifaceted roles of Abp1, the prominent member of fission yeast CENP-Bs, are mediated in part via recognition of a 10-bp AT-rich motif present in most LTRs and require the DNA-binding, transposase, and dimerization domains of Abp1 to maintain transcriptional repression and genome organization. Expression profiling analyses indicated that Abp1 recruits class I/II histone deacetylases (HDACs) to repress Tf2 retrotransposons and genes activated in response to stresses. We demonstrate that class I/II HDACs and sirtuins mediate the clustering of dispersed Tf2 retrotransposons into Tf bodies. Intriguingly, we uncovered an unexpected cooperation between Abp1 and the histone H3K4 methyltransferase Set1 in regulating sense and antisense transcriptional silencing of Tf2 retrotransposons and Tf body integrity. Moreover, Set1-mediated regulation of Tf2 expression and nuclear organization appears to be largely independent of H3K4 methylation. Our study illuminates a molecular pathway involving a transposase-containing transcription factor that cooperates with chromatin modifiers to regulate TE activities.

SUBMITTER: Lorenz DR

PROVIDER: S-EPMC3457346 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CENP-B cooperates with Set1 in bidirectional transcriptional silencing and genome organization of retrotransposons.

Lorenz David R DR Mikheyeva Irina V IV Johansen Peter P Meyer Lauren L Berg Anastasia A Grewal Shiv I S SI Cam Hugh P HP

Molecular and cellular biology 20120820 20

Regulation of transposable elements (TEs) is critical to the integrity of the host genome. The fission yeast Schizosaccharomyces pombe homologs of mammalian CENP-B perform a host genome surveillance role by controlling Tf2 long terminal repeat (LTR) retrotransposons. However, the mechanisms by which CENP-Bs effect their functions are ill defined. Here, we show that the multifaceted roles of Abp1, the prominent member of fission yeast CENP-Bs, are mediated in part via recognition of a 10-bp AT-ri ...[more]

PMID: 22907751

Similar Datasets

Project description:Preclinical and clinical data have highlighted the challenges in targeting KRAS mutant tumors, revealing that cancer cells initially sensitive to treatment circumvent KRAS dependence and become tolerant. However, the exact mechanisms governing the transition from a drug-sensitive to a drug-tolerant state remain unclear. Herein, we used 3D culture models of mutant KRAS colorectal cancer cells with distinct KRAS dependencies to show that sensitive and resistant cells undergo distinct chromatin and transcriptional adaptations upon acute KRAS loss. KRAS-silenced sensitive cells presented G0/G1 cell cycle arrest and exhibited a transcriptional signature characteristic of quiescent cells. Moreover, proteomic profiling underscored common biological processes up-regulated in sensitive cells, including nucleosome assembly, gene expression regulation, and mRNA splicing. A detailed analysis of chromatin features revealed that sensitive cells altered eu/heterochromatin states and gained TADs after KRAS silencing whereas the eu/heterochromatin states of resistant cells remained unchanged, and the number of TADs decreased. Strikingly, only KRAS-silenced sensitive cells displayed alterations in how chromatin organizes into packing domains, displaying a lower domain packing scaling. Chromatin packing scaling regulates the interaction between macromolecular complexes and DNA, thus controlling transcriptional malleability and plasticity. Accordingly, although KRAS-silenced sensitive and resistant cells displayed a transcriptomic profile distinct from their controls, only sensitive cells presented higher variability over time, thus suggesting higher transcriptional plasticity. Overall, our findings provide compelling evidence supporting chromatin 3D reorganization and transcriptional variability in KRAS-silenced sensitive cells. This epigenetic mechanism is likely to underlie the remarkable ability of cancer cells to adapt, persist, and sustain malignancy without oncogenic KRAS.

Dataset Information

CENP-B cooperates with Set1 in bidirectional transcriptional silencing and genome organization of retrotransposons.

Publications

CENP-B cooperates with Set1 in bidirectional transcriptional silencing and genome organization of retrotransposons.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets