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Creativity Motivation – What is motivation – Corey K Katir
Advertising From http://www.creativitymotivation.com Describes motivation process for creativity with emphasis on intrinsic motivation by Corey K Katir Plant resistance to pathogen challenge is thought to be mediated through salicylic acid (SA) signalling; here NPR3 and NPR4, paralogues of the transcription cofactor NPR1, are identified as receptors of SA.
A combination of four transcription factors, GATA4, HAND2, MEF2C and TBX5, can reprogram fibroblasts into cardiac-like myocytes in vitro and in vivo; expression of these factors ameliorated cardiac function in mice that had suffered myocardial infarction.
Sirtuin proteins regulate diverse cellular pathways that influence genomic stability, metabolism and ageing. SIRT7 is a mammalian sirtuin whose biochemical activity, molecular targets and physiological functions have been unclear. Here we show that SIRT7 is an NAD+-dependent H3K18Ac (acetylated lysine 18 of histone H3) deacetylase that stabilizes the transformed state of cancer cells. Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression. The spectrum of SIRT7 target genes is defined in part by its interaction with the cancer-associated E26 transformed specific (ETS) transcription factor ELK4, and comprises numerous genes with links to tumour suppression. Notably, selective hypoacetylation of H3K18Ac has been linked to oncogenic transformation, and in patients is associated with aggressive tumour phenotypes and poor prognosis. We find that deacetylation of H3K18Ac by SIRT7 is necessary for maintaining essential features of human cancer cells, including anchorage-independent growth and escape from contact inhibition. Moreover, SIRT7 is necessary for a global hypoacetylation of H3K18Ac associated with cellular transformation by the viral oncoprotein E1A. Finally, SIRT7 depletion markedly reduces the tumorigenicity of human cancer cell xenografts in mice. Together, our work establishes SIRT7 as a highly selective H3K18Ac deacetylase and demonstrates a pivotal role for SIRT7 in chromatin regulation, cellular transformation programs and tumour formation in vivo.
Evolution of the mammalian sex chromosomes has resulted in a heterologous X and Y pair, where the Y chromosome has lost most of its genes. Hence, there is a need for X-linked gene dosage compensation between XY males and XX females. In placental mammals, this is achieved by random inactivation of one X chromosome in all female somatic cells. Upregulation of Xist transcription on the future inactive X chromosome acts against Tsix antisense transcription, and spreading of Xist RNA in cis triggers epigenetic changes leading to X-chromosome inactivation. Previously, we have shown that the X-encoded E3 ubiquitin ligase RNF12 is upregulated in differentiating mouse embryonic stem cells and activates Xist transcription and X-chromosome inactivation. Here we identify the pluripotency factor REX1 as a key target of RNF12 in the mechanism of X-chromosome inactivation. RNF12 causes ubiquitination and proteasomal degradation of REX1, and Rnf12 knockout embryonic stem cells show an increased level of REX1. Using chromatin immunoprecipitation sequencing, REX1 binding sites were detected in Xist and Tsix regulatory regions. Overexpression of REX1 in female embryonic stem cells was found to inhibit Xist transcription and X-chromosome inactivation, whereas male Rex1+/a embryonic stem cells showed ectopic X-chromosome inactivation. From this, we propose that RNF12 causes REX1 breakdown through dose-dependent catalysis, thereby representing an important pathway to initiate X-chromosome inactivation. Rex1 and Xist are present only in placental mammals, which points to co-evolution of these two genes and X-chromosome inactivation.
Previous work has shown that a combination of three transcription factors can directly reprogram cardiac fibroblasts into cardiomyocyte-like cell in vitro; now, the same authors demonstrate in vivo reprogramming of cardiac fibroblasts into induced cardiomyocytes.
Transcription factors and chromatin modifiers are important in the programming and reprogramming of cellular states during development. Transcription factors bind to enhancer elements and recruit coactivators and chromatin-modifying enzymes to facilitate transcription initiation. During differentiation a subset of these enhancers must be silenced, but the mechanisms underlying enhancer silencing are poorly understood. Here we show that the histone demethylase lysine-specific demethylase 1 (LSD1; ref. 5), which demethylates histone H3 on Lysa4 or Lysa9 (H3K4/K9), is essential in decommissioning enhancers during the differentiation of mouse embryonic stem cells (ESCs). LSD1 occupies enhancers of active genes that are critical for control of the state of ESCs. However, LSD1 is not essential for the maintenance of ESC identity. Instead, ESCs lacking LSD1 activity fail to differentiate fully, and ESC-specific enhancers fail to undergo the histone demethylation events associated with differentiation. At active enhancers, LSD1 is a component of the NuRD (nucleosome remodelling and histone deacetylase) complex, which contains additional subunits that are necessary for ESC differentiation. We propose that the LSD1aNuRD complex decommissions enhancers of the pluripotency program during differentiation, which is essential for the complete shutdown of the ESC gene expression program and the transition to new cell states.
Photosensitivity syndrome brings to light a new transcription-coupled DNA repair cofactor
From feeds.nature Three teams have applied whole-exome and proteome methods to identify a new cofactor of human RNA polymerase II that is required for the recovery of transcription on damaged templates. The identification of this new factor raises questions about the causal relationships between molecular mechanisms of transcription regulation and excision repair and developmental and neurological disease and nonmalignant skin photosensitivity.
Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair
From feeds.nature Tomoo Ogi and colleagues report mutations of UVSSA causing a third complementation group of the UV-sensitive syndrome. UVSSA deficiency results in defective transcription-coupled nucleotide-excision repair and failure to resolve stalled RNA polymerase IIo at DNA damage sites.
Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair
From feeds.nature Kiyoji Tanaka and colleagues report mutations of UVSSA causing a third complementation group of UV-sensitive syndrome. UVSSA deficiency results in defective transcription-coupled nucleotide-excision repair and failure to resolve stalled RNA polymerase IIo at DNA damage sites.
UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair
From feeds.nature Jurgen Marteijn, Wim Vermeulen and colleagues report proteomic identification of UVSSA in a UV-induced protein complex implicated in UV-sensitive syndrome. They show that knockdown of UVSSA impairs trancription-coupled nucleotide-excision repair.
Reshaping of global gene expression networks and sex-biased gene expression by integration of a young gene
From feeds.nature Reshaping of global gene expression networks and sex-biased gene expression by integration of a young geneThe Caf40-derived transcription factor Zeus is found to have rapidly evolved a sex-specific gene regulatory network in Drosophila, illustrating how a newly emerged gene acquires functions and integrates with pre-existing genes.
Chd2 interacts with H3.3 to determine myogenic cell fate
From feeds.nature Chd2 interacts with H3.3 to determine myogenic cell fateThe transcription factor MyoD associates with the chromatin remodelling enzyme chromodomain helicase DNA-binding domain 2 (Chd2), leading to the deposition of the histone variant H3.3 at myogenic regulatory regions prior to their activation during muscle differentiation.
NURDs are required for diversity
From feeds.nature NURD was recently shown to functionally recruit PRC2 to a set of common target genes. A new study in Cell Stem Cell reveals a crucial role for NURD in embryonic stem cell lineage commitment by regulating the transcriptional heterogeneity of pluripotency factors.
Untangling the mysteries of maternal inheritance with polyCOMB
From feeds.nature Deletion of PRC1 components in growing mouse oocytes establishes their crucial function in maternal inheritance by determining chromatin states for the following generation.
A dual function of Bcl11b/Ctip2 in hippocampal neurogenesis
From feeds.nature The transcription factor Bcl11b/Ctip2 promotes hippocampal progenitor proliferation and neural differentiation in a non-cell autonomous manner by regulating the expression of the cell adhesion molecule Desmoplakin. Forebrain-specific ablation causes defective spatial learning and memory.
Structure of a dominant-negative helix-loop-helix transcriptional regulator suggests mechanisms of autoinhibition
From feeds.nature Structure of a dominant-negative helix-loop-helix transcriptional regulator suggests mechanisms of autoinhibitionThe first structural views of an Id-like negative transcription factor, HMM, provide insights into HMM control of, and specificity for, its cognate bHLH transcription factor Olig1.
Evolution of the mammalian sex chromosomes has resulted in a heterologous X and Y pair, where the Y chromosome has lost most of its genes. Hence, there is a need for X-linked gene dosage compensation between XY males and XX females. In placental mammals, this is achieved by random inactivation of one X chromosome in all female somatic cells. Upregulation of Xist transcription on the future inactive X chromosome acts against Tsix antisense transcription, and spreading of Xist RNA in cis triggers epigenetic changes leading to X-chromosome inactivation. Previously, we have shown that the X-encoded E3 ubiquitin ligase RNF12 is upregulated in differentiating mouse embryonic stem cells and activates Xist transcription and X-chromosome inactivation. Here we identify the pluripotency factor REX1 as a key target of RNF12 in the mechanism of X-chromosome inactivation. RNF12 causes ubiquitination and proteasomal degradation of REX1, and Rnf12 knockout embryonic stem cells show an increased level of REX1. Using chromatin immunoprecipitation sequencing, REX1 binding sites were detected in Xist and Tsix regulatory regions. Overexpression of REX1 in female embryonic stem cells was found to inhibit Xist transcription and X-chromosome inactivation, whereas male Rex1+/a embryonic stem cells showed ectopic X-chromosome inactivation. From this, we propose that RNF12 causes REX1 breakdown through dose-dependent catalysis, thereby representing an important pathway to initiate X-chromosome inactivation. Rex1 and Xist are present only in placental mammals, which points to co-evolution of these two genes and X-chromosome inactivation.
Direct interaction of PU.1 with oncogenic transcription factors reduces its serine phosphorylation and promoter binding
From feeds.nature
Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding
From feeds.nature
Small molecule antibody targeting HLA class I inhibits myeloma cancer stem cells by repressing pluripotency-associated transcription factors
From feeds.nature
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Capital Online Revenue Introduces Innovate Business Education Techniques
As an alternative to more traditional methods of learning about business and commerce, Capital Online Revenue introduces a new “earn and learn” training program.
Though business colleges remain in great supply, more and more Americans are turning to alternative sources of training and education, particularly during these days of economic upset and uncertainty. The simple truth is that with layoffs so prevalent and incomes so unsteady, investing in a full-time business education simply isn’t a viable option for many entrepreneurs. Instead, they are looking to business training modules that allow for on-the-job training, providing a way to master the tools of the trade even while making a profit. Capital Online Revenue continues to spearhead this movement with the introduction of its new “earn-and-learn” business training techniques.
Different from both traditional business education courses and even other online endeavors, Capital Online Revenue is a service that extends to customers a wealth of resources for learning about online business. What makes Capital Online Revenue services unique, however, is the fact that its training techniques are implemented in real-time. In other words, customers are both learning about online business and establishing their own online business both at the same time.
Though the notion of a make-money-online opportunity is hardly new, the methods being introduced by Capital Online Revenue are unlike anything yet devised by its competitors. What makes this service different is the emphasis it places on its training aspects. Though the long-term goal is for customers to establish their own online business, this comes hand-in-hand with an array of training resources and materials that include not only tutorial videos, but also a unique training component that includes one-on-one coaching from a team of live experts. Capital Online Revenue extends these services through a variety of media, including online chat, e-mail, and phone.
Capital Online Revenue introduction of these features has already met with enthusiasm from its current customer base. The service continues to define its niche, appealing to retirees, stay-at-home-parents, and working professionals who simply lack the time or resources necessary to attend more conventional business classes.