Biology Reference
In-Depth Information
Chapter 4
Gene Regulatory Networks
Martha L. Bulyk 1 and A.J. Marian Walhout 2
1 Division of Genetics, Department of Medicine; Department of Pathology; Brigham & Women's Hospital and Harvard Medical School, Boston, MA
02115, USA & Harvard-MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115, USA,
2 Programs in
Systems Biology, and Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Chapter Outline
Cells are Computers
65
GRN Edges: Physical Interactions Between TFs and
DNA
Gene Regulation
65
73
Transcription
65
GRNs: Visualization
74
Gene Regulatory Networks (GRN S )
66
GRNs: Data Quality
74
GRN Nodes: Transcription Factors
67
GRN Structure and Function
75
GRN Nodes: Cis-Regulatory Elements
67
GRNs: Model Organisms
79
TF-Binding Sites
69
Future Challenges
81
Cis-Regulatory Modules (CRMs)
69
Acknowledgements
82
References
82
CELLS ARE COMPUTERS
Cells constantly interpret their environment during devel-
opment, in response to different physiological and envi-
ronmental conditions and in disease. In response to various
inputs, they exert appropriate outputs such as proliferation
and differentiation during development, the generation of
defense molecules to combat infection by harmful parasites
or microbes, or the synthesis of hormones such as leptin or
insulin to attain the appropriate physiological state upon
feeding. Cells have evolved a repertoire of sophisticated
regulatory mechanisms that measure and process environ-
mental input in order to exert the appropriate biological
output. One of the most important mechanisms is to
modulate the expression of genes that encode proteins
involved in any of the cellular responses. Understanding
how such differential gene regulation is orchestrated to
deliver a biological output based on a particular input is
a primary focus in the larger field of systems biology.
from a DNA template by an RNA polymerase) and trans-
lation (the subsequent synthesis of a polypeptide from an
RNA template by the ribosome) [1] . The balance between
synthesis and breakdown of both the RNA and the poly-
peptide dictates protein expression levels unique to each cell
in response to different developmental, physiological or
pathological conditions. The human genome contains
~25 000 protein-coding genes, as well as numerous small
and long non-coding RNA genes (see Chapter 2). The total
complement of RNAs encoded by the genome is referred to
as the transcriptome, and the full repertoire of proteins is
called the proteome ( Figure 4.1 B). The two synthesis
processes, transcription and translation, are most pivotal in
gene regulation and are tightly controlled by different types
of regulatory networks. Transcription is regulated by
proteins called transcription factors (TFs) (see below), as
well as by non-coding RNAs, whereas translation is regu-
lated by non-coding RNAs and RNA-binding proteins. In
this chapter, we focus mainly on transcriptional regulation
in the context of gene regulatory networks (GRNs).
GENE REGULATION
The central dogma in molecular biology ( Figure 4.1 A)
depicts the flow of information in the generation of a protein
though transcription (the synthesis of an RNA molecule
TRANSCRIPTION
Transcriptional regulation differs between prokaryotes and
eukaryotes. For
instance,
in contrast
to prokaryotes,
 
 
 
 
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