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Related Concept Videos

Cis-regulatory Sequences02:02

Cis-regulatory Sequences

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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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Master Transcription Regulators02:23

Master Transcription Regulators

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

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Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
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Co-activators and Co-repressors02:04

Co-activators and Co-repressors

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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Transcription01:17

Transcription

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Transcription is the synthesis of RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in correctly synthesizing messenger RNA (mRNA). Transcriptional regulation is responsible for the differentiation of different types of cells and often for the proper cellular response to environmental signals.
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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
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Deconvolution of Nascent Sequencing Data Using Transcriptional Regulatory Elements.

Zachary Maas1, Rutendo Sigauke, Robin Dowell

  • 1Department of Computer Science, BioFrontiers Institute, University of Colorado Boulder, 596 UCB, Boulder, CO 80309, USA, zachary.maas@colorado.edu.

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Summary

This study introduces supervised deconvolution for nascent sequencing data, revealing enhancer RNAs as key features. Simple methods are effective, but undifferentiated cells pose challenges for accurate transcriptional analysis.

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High-throughput Identification of Gene Regulatory Sequences Using Next-generation Sequencing of Circular Chromosome Conformation Capture 4C-seq
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Area of Science:

  • Genomics and Molecular Biology
  • Bioinformatics and Computational Biology

Background:

  • Microdissection of heterogeneous tissues is crucial for biological and biomedical research.
  • Supervised deconvolution for mixed sequencing data was previously limited to RNA-seq and ATAC-seq.

Purpose of the Study:

  • To develop supervised deconvolution methods for nascent sequencing data (GRO-seq, PRO-seq).
  • To identify informative features and assess deconvolution method performance for active transcription analysis.

Main Methods:

  • Applied supervised deconvolution to nascent sequencing data for the first time.
  • Developed a novel filtering method for promoter and enhancer regions.
  • Utilized in-silico mixtures and RNA-seq best practices for validation.

Main Results:

  • Enhancer RNAs were identified as highly informative features for deconvolution.
  • Simpler deconvolution methods generally outperformed complex ones for nascent sequencing data.
  • Undifferentiated cell types significantly confounded deconvolution results due to open chromatin.

Conclusions:

  • Supervised deconvolution of nascent sequencing data is generally feasible.
  • Future approaches may require integration with other sequencing protocols to address challenges with undifferentiated cell types.