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Gene expression rearrangements denoting changes in the biological state.

ABSTRACT: In many situations, the gene expression signature is a unique marker of the biological state. We study the modification of the gene expression distribution function when the biological state of a system experiences a change. This change may be the result of a selective pressure, as in the Long Term Evolution Experiment with E. Coli populations, or the progression to Alzheimer disease in aged brains, or the progression from a normal tissue to the cancer state. The first two cases seem to belong to a class of transitions, where the initial and final states are relatively close to each other, and the distribution function for the differential expressions is short ranged, with a tail of only a few dozens of strongly varying genes. In the latter case, cancer, the initial and final states are far apart and separated by a low-fitness barrier. The distribution function shows a very heavy tail, with thousands of silenced and over-expressed genes. We characterize the biological states by means of their principal component representations, and the expression distribution functions by their maximal and minimal differential expression values and the exponents of the Pareto laws describing the tails.

SUBMITTER: Gonzalez A

PROVIDER: S-EPMC8055689 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Gene expression rearrangements denoting changes in the biological state.

Gonzalez Augusto A Nieves Joan J Leon Dario A DA Bringas Vega Maria Luisa ML Sosa Pedro Valdes PV

Scientific reports 20210419 1

In many situations, the gene expression signature is a unique marker of the biological state. We study the modification of the gene expression distribution function when the biological state of a system experiences a change. This change may be the result of a selective pressure, as in the Long Term Evolution Experiment with E. Coli populations, or the progression to Alzheimer disease in aged brains, or the progression from a normal tissue to the cancer state. The first two cases seem to belong t ...[more]

PMID: 33875699

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Project description:Changes in chromatin accessibility regulate the expression of multiple genes by controlling transcription factor access to key gene regulatory sequences. Here, we sought to establish a potential function for altered chromatin accessibility in control of key gene expression events during lens cell differentiation by establishing genome-wide chromatin accessibility maps specific for four distinct stages of lens cell differentiation and correlating specific changes in chromatin accessibility with genome-wide changes in gene expression. ATAC sequencing was employed to generate chromatin accessibility profiles that were correlated with the expression profiles of over 10,000 lens genes obtained by high-throughput RNA sequencing at the same stages of lens cell differentiation. Approximately 90,000 regions of the lens genome exhibited distinct changes in chromatin accessibility at one or more stages of lens differentiation. Over 1000 genes exhibited high Pearson correlation coefficients (r > 0.7) between altered expression levels at specific stages of lens cell differentiation and changes in chromatin accessibility in potential promoter (-7.5kbp/+2.5kbp of the transcriptional start site) and/or other potential cis-regulatory regions ( ±10 kb of the gene body). Analysis of these regions identified consensus binding sequences for multiple transcription factors including members of the TEAD, FOX, and NFAT families of transcription factors as well as HIF1a, RBPJ and IRF1. Functional mapping of genes with high correlations between altered chromatin accessibility and differentiation state-specific gene expression changes identified multiple families of proteins whose expression could be regulated through changes in chromatin accessibility including those governing lens structure (BFSP1,BFSP2), gene expression (Pax-6, Sox 2), translation (TDRD7), cell-cell communication (GJA1), autophagy (FYCO1), signal transduction (SMAD3, EPHA2), and lens transparency (CRYBB1, CRYBA4). These data provide a novel relationship between altered chromatin accessibility and lens differentiation and they identify a wide-variety of lens genes and functions that could be regulated through altered chromatin accessibility. The data also point to a large number of potential DNA regulatory sequences and transcription factors whose functional analysis is likely to provide insight into novel regulatory mechanisms governing the lens differentiation program.

Dataset Information

Gene expression rearrangements denoting changes in the biological state.

Publications

Gene expression rearrangements denoting changes in the biological state.

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