Targeting the Transcriptome Through Globally Acting Components

Transcription is a step in gene expression that defines the identity of cells and its dysregulation is associated with diseases. With advancing technologies revealing molecular underpinnings of the cell with ever-higher precision, our ability to view the transcriptomes may have surpassed our knowledge of the principles behind their organization. The human RNA polymerase II (Pol II) machinery comprises thousands of components that, in conjunction with epigenetic and other mechanisms, drive specialized programs of development, differentiation, and responses to the environment. Parts of these programs are repurposed in oncogenic transformation. Targeting of cancers is commonly done by inhibiting general or broadly acting components of the cellular machinery. The critical unanswered question is how globally acting or general factors exert cell type specific effects on transcription. One solution, which is discussed here, may be among the events that take place at genes during early Pol II transcription elongation. This essay turns the spotlight on the well-known phenomenon of promoter-proximal Pol II pausing as a step that separates signals that establish pausing genome-wide from those that release the paused Pol II into the gene. Concepts generated in this rapidly developing field will enhance our understanding of basic principles behind transcriptome organization and hopefully translate into better therapies at the bedside.

IMPLEMENTASI ALAT PERAGA EDUKASI PIPLAS (PIPET PLASTIK) UNTUK MENINGKATKAN PEMAHAMAN IPA PADA SISWA DI SMP NEGERI 1 GANGGA

The study aims to increase the understanding of gene concepts and inheritance by providing a more concrete representation of the genes. The design of this research uses the quantitative approach of experimentation. Subjects and objects of study are students of grade IX-5 SMP Negeri 1 Gangga, amounting to 29 not one person until a total of 28 people. This Piplas educational tool is very simple because it only makes use of plastic pipettes used by ice-drinking students. Usually plastic pipettes are used for crafting, but are used to provide a concrete representation of the genes. The results showed that most students are easier to understand the concept of genes, capable of making crosses easily so as to improve learning outcomes. Tests were given before learning obtained an average value of 30.79 and after learning obtained an average value of 69.4 an increase of 125.4%.

Early in life effects and heredity: reconciling neo-Darwinism with neo-Lamarckism under the banner of the inclusive evolutionary synthesis

Recent discoveries show that early in life effects often have long-lasting influences, sometimes even spanning several generations. Such intergenerational effects of early life events appear not easily reconcilable with strict genetic inheritance. However, an integrative evolutionary medicine of early life effects needs a sound view of inheritance in development and evolution. Here, we show how to articulate the gene-centred and non-gene-centred visions of inheritance. We first recall the coexistence of two gene concepts in scientific discussions, a statistical one (focused on patterns of parent–offspring resemblance, and implicitly including non-DNA-sequence-based resemblance), and a molecular one (based on the DNA sequence). We then show how all the different mechanisms of inheritance recently discovered can be integrated into an inclusive theory of evolution where different mechanisms would enable adaptation to changing environments at different timescales. One surprising consequence of this integrative vision of inheritance is that early in life effects start much earlier than fertilization.This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.