A Mathematical Model for Enhancer Activation Kinetics During Cell Differentiation

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Abstract

Cell differentiation and development are for a great part steered by cell type specific enhancers. Transcription factor (TF) binding to an enhancer together with DNA looping result in transcription initiation. In addition to binding motifs for TFs, enhancer regions typically contain specific histone modifications. This information has been used to detect enhancer regions and classify them into different subgroups. However, it is poorly understood how TF binding and histone modifications are causally connected and what kind of molecular dynamics steer the activation process. Contrary to previous studies, we do not treat the activation events as static epigenetic marks but consider the enhancer activation as a dynamic process. We develop a mathematical model to describe the dynamic mechanisms between TF binding and histone modifications known to characterize an active enhancer. We estimate model parameters from time-course data and infer the causal relationships between TF binding and different histone modifications. We benchmark the performance of this framework using simulated data and survey the ability of our method to identify the correct model structures for a variety of system dynamics, noise levels and the number of measurement time points.

Details

Original languageEnglish
Title of host publicationAlgorithms for Computational Biology - 6th International Conference, AlCoB 2019, Proceedings
EditorsMiguel A. Vega-Rodríguez, Ian Holmes, Carlos Martín-Vide
Publication statusPublished - 1 Jan 2019
MoE publication typeA4 Article in a conference publication
EventInternational Conference on Algorithms for Computational Biology - Berkeley, United States
Duration: 28 May 201930 May 2019
Conference number: 6

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
PublisherSpringer
Volume11488 LNBI
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Conference

ConferenceInternational Conference on Algorithms for Computational Biology
Abbreviated titleAlCoB
CountryUnited States
CityBerkeley
Period28/05/201930/05/2019

    Research areas

  • Cell differentiation, Dynamic modeling, Enhancer activation

ID: 34394065