47,546 research outputs found
Transcriptional Regulation: a Genomic Overview
The availability of the Arabidopsis thaliana genome sequence allows a comprehensive analysis of transcriptional regulation in plants using novel genomic approaches and methodologies. Such a genomic view of transcription first necessitates the compilation of lists of elements. Transcription factors are the most numerous of the different types of proteins involved in transcription in eukaryotes, and the Arabidopsis genome codes for more than 1,500 of them, or approximately 6% of its total number of genes. A genome-wide comparison of transcription factors across the three eukaryotic kingdoms reveals the evolutionary generation of diversity in the components of the regulatory machinery of transcription. However, as illustrated by Arabidopsis, transcription in plants follows similar basic principles and logic to those in animals and fungi. A global view and understanding of transcription at a cellular and organismal level requires the characterization of the Arabidopsis transcriptome and promoterome, as well as of the interactome, the localizome, and the phenome of the proteins involved in transcription
Minor Loops in Major Folds: Enhancer-Promoter Looping, Chromatin Restructuring, and Their Association with Transcriptional Regulation and Disease.
The organization and folding of chromatin within the nucleus can determine the outcome of gene expression. Recent technological advancements have enabled us to study chromatin interactions in a genome-wide manner at high resolution. These studies have increased our understanding of the hierarchy and dynamics of chromatin domains that facilitate cognate enhancer-promoter looping, defining the transcriptional program of different cell types. In this review, we focus on vertebrate chromatin long-range interactions as they relate to transcriptional regulation. In addition, we describe how the alteration of boundaries that mark discrete regions in the genome with high interaction frequencies within them, called topological associated domains (TADs), could lead to various phenotypes, including human diseases, which we term as "TADopathies.
Allosteric Modulators of Steroid Hormone Receptors : Structural Dynamics and Gene Regulation
Peer reviewedPublisher PD
Epigenetic aberrations and cancer
The correlation between epigenetic aberrations and disease underscores the importance of epigenetic mechanisms. Here, we review recent findings regarding chromatin modifications and their relevance to cancer
Hierarchy and Feedback in the Evolution of the E. coli Transcription Network
The E.coli transcription network has an essentially feedforward structure,
with, however, abundant feedback at the level of self-regulations. Here, we
investigate how these properties emerged during evolution. An assessment of the
role of gene duplication based on protein domain architecture shows that (i)
transcriptional autoregulators have mostly arisen through duplication, while
(ii) the expected feedback loops stemming from their initial cross-regulation
are strongly selected against. This requires a divergent coevolution of the
transcription factor DNA-binding sites and their respective DNA cis-regulatory
regions. Moreover, we find that the network tends to grow by expansion of the
existing hierarchical layers of computation, rather than by addition of new
layers. We also argue that rewiring of regulatory links due to
mutation/selection of novel transcription factor/DNA binding interactions
appears not to significantly affect the network global hierarchy, and that
horizontally transferred genes are mainly added at the bottom, as new target
nodes. These findings highlight the important evolutionary roles of both
duplication and selective deletion of crosstalks between autoregulators in the
emergence of the hierarchical transcription network of E.coli.Comment: to appear in PNA
Modelling the evolution of transcription factor binding preferences in complex eukaryotes
Transcription factors (TFs) exert their regulatory action by binding to DNA
with specific sequence preferences. However, different TFs can partially share
their binding sequences due to their common evolutionary origin. This
`redundancy' of binding defines a way of organizing TFs in `motif families' by
grouping TFs with similar binding preferences. Since these ultimately define
the TF target genes, the motif family organization entails information about
the structure of transcriptional regulation as it has been shaped by evolution.
Focusing on the human TF repertoire, we show that a one-parameter evolutionary
model of the Birth-Death-Innovation type can explain the TF empirical
ripartition in motif families, and allows to highlight the relevant
evolutionary forces at the origin of this organization. Moreover, the model
allows to pinpoint few deviations from the neutral scenario it assumes: three
over-expanded families (including HOX and FOX genes), a set of `singleton' TFs
for which duplication seems to be selected against, and a higher-than-average
rate of diversification of the binding preferences of TFs with a Zinc Finger
DNA binding domain. Finally, a comparison of the TF motif family organization
in different eukaryotic species suggests an increase of redundancy of binding
with organism complexity.Comment: 14 pages, 5 figures. Minor changes. Final version, accepted for
publicatio
A creature with a hundred waggly tails: intrinsically disordered proteins in the ribosome
This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Intrinsic disorder (i.e., lack of a unique 3-D structure) is a common phenomenon, and many biologically active proteins are disordered as a whole, or contain long disordered regions. These intrinsically disordered proteins/regions constitute a significant part of all proteomes, and their functional repertoire is complementary to functions of ordered proteins. In fact, intrinsic disorder represents an important driving force for many specific functions. An illustrative example of such disorder-centric functional class is RNA-binding proteins. In this study, we present the results of comprehensive bioinformatics analyses of the abundance and roles of intrinsic disorder in 3,411 ribosomal proteins from 32 species. We show that many ribosomal proteins are intrinsically disordered or hybrid proteins that contain ordered and disordered domains. Predicted globular domains of many ribosomal proteins contain noticeable regions of intrinsic disorder. We also show that disorder in ribosomal proteins has different characteristics compared to other proteins that interact with RNA and DNA including overall abundance, evolutionary conservation, and involvement in protein–protein interactions. Furthermore, intrinsic disorder is not only abundant in the ribosomal proteins, but we demonstrate that it is absolutely necessary for their various functions
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