Comparative functional genomics revealed conservation and diversification of three enhancers of the isl1 gene for motor and sensory neuron-specific expression

Osamu Uemura, Yohei Okada, Hideki Ando, Mickael Guedj, Shin Ichi Higashijima, Takuya Shimazaki, Naoichi Chino, Hideyuki Okano, Hitoshi Okamoto

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Islet-1 (Isl1) is a member of the Isl1 family of LIM-homeodomain transcription factors (LIM-HD) that is expressed in a defined subset of motor and sensory neurons during vertebrate embryogenesis. To investigate how this specific expression of isl1 is regulated, we searched for enhancers of the isl1 gene that are conserved in vertebrate evolution. Initially, two enhancer elements, CREST1 and CREST2, were identified downstream of the isl1 locus in the genomes of fugu, chick, mouse, and human by BLAST searching for highly similar elements to those originally identified as motor and sensory neuron-specific enhancers in the zebrafish genome. The combined action of these elements is sufficient for completely recapitulating the subtype-specific expression of the isl1 gene in motor neurons of the mouse spinal cord. Furthermore, by direct comparison of the upstream flanking regions of the zebrafish and human isl1 genes, we identified another highly conserved noncoding element, CREST3, and subsequently C3R, a similar element to CREST3 with two CDP CR1 recognition motifs, in the upstream regions of all other isl1 family members. In mouse and human, CRESTs are located as far as more than 300 kb away from the isl1 locus, while they are much closer to the isl1 locus in zebrafish. Although all of zebrafish CREST2, CREST3, and C3R activate gene expression in the sensory neurons of zebrafish, CREST2 of mouse and human does not have the sequence necessary for sensory neuron-specific expression. Our results revealed both a remarkable conservation of the regulatory elements regulating subtype-specific gene expression in motor and sensory neurons and the dynamic process of reorganization of these elements whereby each element increases the level of cell-type specificity by losing redundant functions with the other elements during vertebrate evolution.

Original languageEnglish
Pages (from-to)587-606
Number of pages20
JournalDevelopmental Biology
Volume278
Issue number2
DOIs
Publication statusPublished - 2005 Feb 15

Fingerprint

Motor Neurons
Zebrafish
Sensory Receptor Cells
Genomics
Vertebrates
Genes
Gene Expression
Takifugu
Genome
Cytidine Diphosphate
Embryonic Development
Spinal Cord
Transcription Factors

Keywords

  • Comparative functional genomics
  • Enhancer
  • Islet-1
  • Islet-2
  • Islet-3
  • Motor neuron
  • Mouse
  • Sensory neuron
  • Subtype specification
  • Zebrafish

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Comparative functional genomics revealed conservation and diversification of three enhancers of the isl1 gene for motor and sensory neuron-specific expression. / Uemura, Osamu; Okada, Yohei; Ando, Hideki; Guedj, Mickael; Higashijima, Shin Ichi; Shimazaki, Takuya; Chino, Naoichi; Okano, Hideyuki; Okamoto, Hitoshi.

In: Developmental Biology, Vol. 278, No. 2, 15.02.2005, p. 587-606.

Research output: Contribution to journalArticle

Uemura, Osamu ; Okada, Yohei ; Ando, Hideki ; Guedj, Mickael ; Higashijima, Shin Ichi ; Shimazaki, Takuya ; Chino, Naoichi ; Okano, Hideyuki ; Okamoto, Hitoshi. / Comparative functional genomics revealed conservation and diversification of three enhancers of the isl1 gene for motor and sensory neuron-specific expression. In: Developmental Biology. 2005 ; Vol. 278, No. 2. pp. 587-606.
@article{e5a1182c6b294cdbbff11b9b45428bc1,
title = "Comparative functional genomics revealed conservation and diversification of three enhancers of the isl1 gene for motor and sensory neuron-specific expression",
abstract = "Islet-1 (Isl1) is a member of the Isl1 family of LIM-homeodomain transcription factors (LIM-HD) that is expressed in a defined subset of motor and sensory neurons during vertebrate embryogenesis. To investigate how this specific expression of isl1 is regulated, we searched for enhancers of the isl1 gene that are conserved in vertebrate evolution. Initially, two enhancer elements, CREST1 and CREST2, were identified downstream of the isl1 locus in the genomes of fugu, chick, mouse, and human by BLAST searching for highly similar elements to those originally identified as motor and sensory neuron-specific enhancers in the zebrafish genome. The combined action of these elements is sufficient for completely recapitulating the subtype-specific expression of the isl1 gene in motor neurons of the mouse spinal cord. Furthermore, by direct comparison of the upstream flanking regions of the zebrafish and human isl1 genes, we identified another highly conserved noncoding element, CREST3, and subsequently C3R, a similar element to CREST3 with two CDP CR1 recognition motifs, in the upstream regions of all other isl1 family members. In mouse and human, CRESTs are located as far as more than 300 kb away from the isl1 locus, while they are much closer to the isl1 locus in zebrafish. Although all of zebrafish CREST2, CREST3, and C3R activate gene expression in the sensory neurons of zebrafish, CREST2 of mouse and human does not have the sequence necessary for sensory neuron-specific expression. Our results revealed both a remarkable conservation of the regulatory elements regulating subtype-specific gene expression in motor and sensory neurons and the dynamic process of reorganization of these elements whereby each element increases the level of cell-type specificity by losing redundant functions with the other elements during vertebrate evolution.",
keywords = "Comparative functional genomics, Enhancer, Islet-1, Islet-2, Islet-3, Motor neuron, Mouse, Sensory neuron, Subtype specification, Zebrafish",
author = "Osamu Uemura and Yohei Okada and Hideki Ando and Mickael Guedj and Higashijima, {Shin Ichi} and Takuya Shimazaki and Naoichi Chino and Hideyuki Okano and Hitoshi Okamoto",
year = "2005",
month = "2",
day = "15",
doi = "10.1016/j.ydbio.2004.11.031",
language = "English",
volume = "278",
pages = "587--606",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Comparative functional genomics revealed conservation and diversification of three enhancers of the isl1 gene for motor and sensory neuron-specific expression

AU - Uemura, Osamu

AU - Okada, Yohei

AU - Ando, Hideki

AU - Guedj, Mickael

AU - Higashijima, Shin Ichi

AU - Shimazaki, Takuya

AU - Chino, Naoichi

AU - Okano, Hideyuki

AU - Okamoto, Hitoshi

PY - 2005/2/15

Y1 - 2005/2/15

N2 - Islet-1 (Isl1) is a member of the Isl1 family of LIM-homeodomain transcription factors (LIM-HD) that is expressed in a defined subset of motor and sensory neurons during vertebrate embryogenesis. To investigate how this specific expression of isl1 is regulated, we searched for enhancers of the isl1 gene that are conserved in vertebrate evolution. Initially, two enhancer elements, CREST1 and CREST2, were identified downstream of the isl1 locus in the genomes of fugu, chick, mouse, and human by BLAST searching for highly similar elements to those originally identified as motor and sensory neuron-specific enhancers in the zebrafish genome. The combined action of these elements is sufficient for completely recapitulating the subtype-specific expression of the isl1 gene in motor neurons of the mouse spinal cord. Furthermore, by direct comparison of the upstream flanking regions of the zebrafish and human isl1 genes, we identified another highly conserved noncoding element, CREST3, and subsequently C3R, a similar element to CREST3 with two CDP CR1 recognition motifs, in the upstream regions of all other isl1 family members. In mouse and human, CRESTs are located as far as more than 300 kb away from the isl1 locus, while they are much closer to the isl1 locus in zebrafish. Although all of zebrafish CREST2, CREST3, and C3R activate gene expression in the sensory neurons of zebrafish, CREST2 of mouse and human does not have the sequence necessary for sensory neuron-specific expression. Our results revealed both a remarkable conservation of the regulatory elements regulating subtype-specific gene expression in motor and sensory neurons and the dynamic process of reorganization of these elements whereby each element increases the level of cell-type specificity by losing redundant functions with the other elements during vertebrate evolution.

AB - Islet-1 (Isl1) is a member of the Isl1 family of LIM-homeodomain transcription factors (LIM-HD) that is expressed in a defined subset of motor and sensory neurons during vertebrate embryogenesis. To investigate how this specific expression of isl1 is regulated, we searched for enhancers of the isl1 gene that are conserved in vertebrate evolution. Initially, two enhancer elements, CREST1 and CREST2, were identified downstream of the isl1 locus in the genomes of fugu, chick, mouse, and human by BLAST searching for highly similar elements to those originally identified as motor and sensory neuron-specific enhancers in the zebrafish genome. The combined action of these elements is sufficient for completely recapitulating the subtype-specific expression of the isl1 gene in motor neurons of the mouse spinal cord. Furthermore, by direct comparison of the upstream flanking regions of the zebrafish and human isl1 genes, we identified another highly conserved noncoding element, CREST3, and subsequently C3R, a similar element to CREST3 with two CDP CR1 recognition motifs, in the upstream regions of all other isl1 family members. In mouse and human, CRESTs are located as far as more than 300 kb away from the isl1 locus, while they are much closer to the isl1 locus in zebrafish. Although all of zebrafish CREST2, CREST3, and C3R activate gene expression in the sensory neurons of zebrafish, CREST2 of mouse and human does not have the sequence necessary for sensory neuron-specific expression. Our results revealed both a remarkable conservation of the regulatory elements regulating subtype-specific gene expression in motor and sensory neurons and the dynamic process of reorganization of these elements whereby each element increases the level of cell-type specificity by losing redundant functions with the other elements during vertebrate evolution.

KW - Comparative functional genomics

KW - Enhancer

KW - Islet-1

KW - Islet-2

KW - Islet-3

KW - Motor neuron

KW - Mouse

KW - Sensory neuron

KW - Subtype specification

KW - Zebrafish

UR - http://www.scopus.com/inward/record.url?scp=12944307837&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12944307837&partnerID=8YFLogxK

U2 - 10.1016/j.ydbio.2004.11.031

DO - 10.1016/j.ydbio.2004.11.031

M3 - Article

C2 - 15680372

AN - SCOPUS:12944307837

VL - 278

SP - 587

EP - 606

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 2

ER -