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Showing papers in "Molecular Cell in 2010"


Journal ArticleDOI
TL;DR: It is demonstrated in macrophages and B cells that collaborative interactions of the common factor PU.1 with small sets of macrophage- or B cell lineage-determining transcription factors establish cell-specific binding sites that are associated with the majority of promoter-distal H3K4me1-marked genomic regions.

9,620 citations


Journal ArticleDOI
TL;DR: This review will focus on how the DDR controls DNA repair and the phenotypic consequences of defects in these critical regulatory functions in mammals.

3,678 citations


Journal ArticleDOI
TL;DR: Autophagy is a cell biological process that is a central component of the integrated stress response and can be integrated with other cellular stress responses through parallel stimulation of autophagy and other stress responses by specific stress stimuli.

3,002 citations


Journal ArticleDOI
TL;DR: In mammals, the primary transcriptional response to hypoxic stress is mediated by the hypoxia-inducible factors, and the HIFα subunits are intricately responsive to numerous other factors, including factor-inhibiting HIF1α, sirtuins, and metabolites.

1,919 citations


Journal ArticleDOI
TL;DR: Evidence is provided for a role for the long nuclear-retained regulatory RNA, MALAT1 in AS regulation and for the role for an nrRNA in the regulation of gene expression, which suggests that MALat1 regulates AS by modulating the levels of active SR proteins.

1,893 citations


Journal ArticleDOI
TL;DR: This Review summarizes the concepts of the protective Hsp network, and the most conserved Hsps are molecular chaperones that prevent the formation of nonspecific protein aggregates and assist proteins in the acquisition of their native structures.

1,570 citations


Journal ArticleDOI
TL;DR: It is demonstrated that mTORC1 activation is sufficient to stimulate specific metabolic pathways, including glycolysis, the oxidative arm of the pentose phosphate pathway, and de novo lipid biosynthesis, through the activation of a transcriptional program affecting metabolic gene targets of hypoxia-inducible factor and sterol regulatory element-binding protein.

1,507 citations


Journal ArticleDOI
TL;DR: The mechanisms and functions of the BCL-2 family are discussed in the context of these pathways, highlighting the complex integration and regulation of the b cell CLL/lymphoma-2family in cell fate decisions.

1,353 citations


Journal ArticleDOI
TL;DR: In this article, the authors found that chromobox 7 (CBX7) within the polycomb repressive complex 1 binds to ANRIL, and both CBX7 and ANrIL are found at elevated levels in prostate cancer tissues.

1,326 citations


Journal ArticleDOI
TL;DR: It is reported that secreted miRNAs can serve as signaling molecules mediating intercellular communication and demonstrate that cells can secrete miRNA and deliver them into recipient cells where the exogenous mi RNAs can regulate target gene expression and recipient cell function.

1,122 citations


Journal ArticleDOI
TL;DR: In this paper, the authors focus on the key components of the mTOR complex 1 pathway and how various stresses impinge upon them and how they are implicated in the progression of stress-associated phenotypes and diseases, such as aging, tumorigenesis, and diabetes.

Journal ArticleDOI
TL;DR: A RIP-seq method is developed to capture thePRC2 transcriptome and identify a genome-wide pool of >9000 PRC2-interacting RNAs in embryonic stem cells, some of which may be used as biomarkers and therapeutic targets for human disease.

Journal ArticleDOI
TL;DR: High-resolution maps of genome-nuclear lamina interactions during subsequent differentiation of mouse embryonic stem cells via lineage-committed neural precursor cells into terminally differentiated astrocytes suggest that lamina-genome interactions are widely involved in the control of gene expression programs during lineage commitment and terminal differentiation.

Journal ArticleDOI
TL;DR: Nucleolar function in the stress-induced regulation of p53 and the specific changes in nucleolar morphology and composition that occur upon stress are reviewed.

Journal ArticleDOI
TL;DR: It is shown that sublethal levels of bactericidal antibiotics induce mutagenesis, resulting in heterogeneous increases in the minimum inhibitory concentration for a range of antibiotics, irrespective of the drug target.

Journal ArticleDOI
TL;DR: Infestation of Sirt3⁻/⁻ MEFs with lenti-MnSOD(K122-R) inhibited in vitro immortalization by an oncogene (Ras), inhibited IR-induced genomic instability, and decreased mitochondrial superoxide, suggesting acetylation directly regulates function.

Journal ArticleDOI
TL;DR: STAT3 is not only a downstream target of IL-6 but, with MiR-21, miR-181b-1, PTEN, and CYLD, is part of the positive feedback loop that underlies the epigenetic switch that links inflammation to cancer.

Journal ArticleDOI
TL;DR: The abundant nuclear enzyme PARP-1, a multifunctional regulator of chromatin structure, transcription, and genomic integrity, plays key roles in a wide variety of processes in the nucleus.

Journal ArticleDOI
TL;DR: This work has shown that miRNAs play key roles in fundamental cellular processes, including how cells respond to changes in environment or stresses, and dysregulation of these processes contributes to chronic diseases, including cancers.

Journal ArticleDOI
TL;DR: The XRCC3 protein, which is required for RAD51 foci formation, is also required for replication restart of HU-stalled forks, suggesting that RAD51-mediated strand invasion supports fork restart.

Journal ArticleDOI
TL;DR: The results suggest that crosstalk between oxygen- and redox-responsive signal transducers occurs through the SIRT1-HIF-1alpha interaction.

Journal ArticleDOI
TL;DR: The data argue that MeCP2 may not act as a gene-specific transcriptional repressor in neurons, but might instead dampen transcriptional noise genome-wide in a DNA methylation-dependent manner.

Journal ArticleDOI
TL;DR: These studies provide direct evidence for the existence of high-Ca(2+) microdomains between the ER and mitochondria and suggest an optimal gap width for efficient Ca( 2+) transfer.

Journal ArticleDOI
TL;DR: In this article, the authors identify a class of miRNA target sites that lack both perfect seed pairing and 3'-compensatory pairing and instead have 11-12 contiguous Watson-Crick pairs to the center of the miRNA.

Journal ArticleDOI
TL;DR: It is demonstrated that lmiRNAs direct DNA methylation at loci from which they are produced as well as in trans at their target genes and play roles in gene regulation.

Journal ArticleDOI
TL;DR: Recent studies that shed light on how multiple steps in the miRNA biogenesis pathway are regulated to modulate miRNA function in animals are discussed.

Journal ArticleDOI
TL;DR: It is suggested that Ring1B-mediated chromatin compaction acts to directly limit transcription in vivo and to restore a compact chromatin state and to repress Hox gene expression is not dependent on its histone ubiquitination activity.

Journal ArticleDOI
TL;DR: Biochemical activities of the MCM AAA+ motor are altered and enhanced through such associations: ATP hydrolysis rates are elevated by two orders of magnitude, helicase activity is robust on circular templates, and affinity for DNA substrates is improved.

Journal ArticleDOI
TL;DR: Knockdown of AFF4 in leukemic cells shows reduction in MLL chimera target gene expression, suggesting that AFF 4/SEC could be a key regulator in the pathogenesis of leukemia through many of the MLL partners.

Journal ArticleDOI
TL;DR: In this article, the authors demonstrate that Aurora B kinase phosphorylates three spatially distinct targets within the conserved outer kinetochore KNL1/Mis12 complex/Ndc80 complex (KMN) network.