CREB-binding protein (CBP) gene family regulates planarian survival and stem cell differentiation

Susanna Fraguas; Sheila Cárcel; Coral Vivancos; Ma Dolores Molina; Jordi Ginés; Judith Mazariegos; Thileepan Sekaran; Kerstin Bartscherer; Rafael Romero; Francesc Cebrià

doi:10.1016/j.ydbio.2021.02.008

CREB-binding protein (CBP) gene family regulates planarian survival and stem cell differentiation

Susanna Fraguas, Sheila Cárcel, Coral Vivancos, Ma Dolores Molina, Jordi Ginés, Judith Mazariegos, Thileepan Sekaran, Kerstin Bartscherer, Rafael Romero, Francesc Cebrià

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

14 Citations (Scopus)

Abstract

In developmental biology, the regulation of stem cell plasticity and differentiation remains an open question. CBP(CREB-binding protein)/p300 is a conserved gene family that functions as a transcriptional co-activator and plays important roles in a wide range of cellular processes, including cell death, the DNA damage response, and tumorigenesis. The acetyl transferase activity of CBPs is particularly important, as histone and non-histone acetylation results in changes in chromatin architecture and protein activity that affect gene expression. Many studies have described the conserved functions of CBP/p300 in stem cell proliferation and differentiation. The planarian Schmidtea mediterranea is an excellent model for the in vivo study of the molecular mechanisms underlying stem cell differentiation during regeneration. However, how this process is regulated genetically and epigenetically is not well-understood yet. We identified 5 distinct Smed-cbp genes in S. mediterranea that show different expression patterns. Functional analyses revealed that Smed-cbp-2 appears to be essential for stem cell maintenance. On the other hand, the silencing of Smed-cbp-3 resulted in the growth of blastemas that were apparently normal, but remained largely unpigmented and undifferentiated. Smed-cbp-3 silencing also affected the differentiation of several cell lineages including neural, epidermal, digestive, and excretory cell types. Finally, we analysed the predicted interactomes of CBP-2 and CBP-3 as an initial step to better understand their functions in planarian stem cell biology. Our results indicate that planarian cbp genes play key roles in stem cell maintenance and differentiation.

Original language	English
Pages (from-to)	53-67
Number of pages	15
Journal	Developmental Biology
Volume	476
DOIs	https://doi.org/10.1016/j.ydbio.2021.02.008
Publication status	Published - Aug 2021

Keywords

Animals
CREB-Binding Protein/genetics
Cell Differentiation/genetics
Cell Proliferation
Chromatin/metabolism
Histones/metabolism
Planarians/genetics
Regeneration/genetics
Stem Cells/cytology
Transcription Factors/metabolism

Access to Document

10.1016/j.ydbio.2021.02.008

Cite this

@article{49172dbfe10d4aa7a1439ddb7ca30808,

title = "CREB-binding protein (CBP) gene family regulates planarian survival and stem cell differentiation",

abstract = "In developmental biology, the regulation of stem cell plasticity and differentiation remains an open question. CBP(CREB-binding protein)/p300 is a conserved gene family that functions as a transcriptional co-activator and plays important roles in a wide range of cellular processes, including cell death, the DNA damage response, and tumorigenesis. The acetyl transferase activity of CBPs is particularly important, as histone and non-histone acetylation results in changes in chromatin architecture and protein activity that affect gene expression. Many studies have described the conserved functions of CBP/p300 in stem cell proliferation and differentiation. The planarian Schmidtea mediterranea is an excellent model for the in vivo study of the molecular mechanisms underlying stem cell differentiation during regeneration. However, how this process is regulated genetically and epigenetically is not well-understood yet. We identified 5 distinct Smed-cbp genes in S. mediterranea that show different expression patterns. Functional analyses revealed that Smed-cbp-2 appears to be essential for stem cell maintenance. On the other hand, the silencing of Smed-cbp-3 resulted in the growth of blastemas that were apparently normal, but remained largely unpigmented and undifferentiated. Smed-cbp-3 silencing also affected the differentiation of several cell lineages including neural, epidermal, digestive, and excretory cell types. Finally, we analysed the predicted interactomes of CBP-2 and CBP-3 as an initial step to better understand their functions in planarian stem cell biology. Our results indicate that planarian cbp genes play key roles in stem cell maintenance and differentiation.",

keywords = "Animals, CREB-Binding Protein/genetics, Cell Differentiation/genetics, Cell Proliferation, Chromatin/metabolism, Histones/metabolism, Planarians/genetics, Regeneration/genetics, Stem Cells/cytology, Transcription Factors/metabolism",

author = "Susanna Fraguas and Sheila C{\'a}rcel and Coral Vivancos and Molina, {Ma Dolores} and Jordi Gin{\'e}s and Judith Mazariegos and Thileepan Sekaran and Kerstin Bartscherer and Rafael Romero and Francesc Cebri{\`a}",

year = "2021",

month = aug,

doi = "10.1016/j.ydbio.2021.02.008",

language = "English",

volume = "476",

pages = "53--67",

journal = "Developmental Biology",

issn = "0012-1606",

publisher = "Academic Press",

}

TY - JOUR

T1 - CREB-binding protein (CBP) gene family regulates planarian survival and stem cell differentiation

AU - Fraguas, Susanna

AU - Cárcel, Sheila

AU - Vivancos, Coral

AU - Molina, Ma Dolores

AU - Ginés, Jordi

AU - Mazariegos, Judith

AU - Sekaran, Thileepan

AU - Bartscherer, Kerstin

AU - Romero, Rafael

AU - Cebrià, Francesc

PY - 2021/8

Y1 - 2021/8

N2 - In developmental biology, the regulation of stem cell plasticity and differentiation remains an open question. CBP(CREB-binding protein)/p300 is a conserved gene family that functions as a transcriptional co-activator and plays important roles in a wide range of cellular processes, including cell death, the DNA damage response, and tumorigenesis. The acetyl transferase activity of CBPs is particularly important, as histone and non-histone acetylation results in changes in chromatin architecture and protein activity that affect gene expression. Many studies have described the conserved functions of CBP/p300 in stem cell proliferation and differentiation. The planarian Schmidtea mediterranea is an excellent model for the in vivo study of the molecular mechanisms underlying stem cell differentiation during regeneration. However, how this process is regulated genetically and epigenetically is not well-understood yet. We identified 5 distinct Smed-cbp genes in S. mediterranea that show different expression patterns. Functional analyses revealed that Smed-cbp-2 appears to be essential for stem cell maintenance. On the other hand, the silencing of Smed-cbp-3 resulted in the growth of blastemas that were apparently normal, but remained largely unpigmented and undifferentiated. Smed-cbp-3 silencing also affected the differentiation of several cell lineages including neural, epidermal, digestive, and excretory cell types. Finally, we analysed the predicted interactomes of CBP-2 and CBP-3 as an initial step to better understand their functions in planarian stem cell biology. Our results indicate that planarian cbp genes play key roles in stem cell maintenance and differentiation.

AB - In developmental biology, the regulation of stem cell plasticity and differentiation remains an open question. CBP(CREB-binding protein)/p300 is a conserved gene family that functions as a transcriptional co-activator and plays important roles in a wide range of cellular processes, including cell death, the DNA damage response, and tumorigenesis. The acetyl transferase activity of CBPs is particularly important, as histone and non-histone acetylation results in changes in chromatin architecture and protein activity that affect gene expression. Many studies have described the conserved functions of CBP/p300 in stem cell proliferation and differentiation. The planarian Schmidtea mediterranea is an excellent model for the in vivo study of the molecular mechanisms underlying stem cell differentiation during regeneration. However, how this process is regulated genetically and epigenetically is not well-understood yet. We identified 5 distinct Smed-cbp genes in S. mediterranea that show different expression patterns. Functional analyses revealed that Smed-cbp-2 appears to be essential for stem cell maintenance. On the other hand, the silencing of Smed-cbp-3 resulted in the growth of blastemas that were apparently normal, but remained largely unpigmented and undifferentiated. Smed-cbp-3 silencing also affected the differentiation of several cell lineages including neural, epidermal, digestive, and excretory cell types. Finally, we analysed the predicted interactomes of CBP-2 and CBP-3 as an initial step to better understand their functions in planarian stem cell biology. Our results indicate that planarian cbp genes play key roles in stem cell maintenance and differentiation.

KW - Animals

KW - CREB-Binding Protein/genetics

KW - Cell Differentiation/genetics

KW - Cell Proliferation

KW - Chromatin/metabolism

KW - Histones/metabolism

KW - Planarians/genetics

KW - Regeneration/genetics

KW - Stem Cells/cytology

KW - Transcription Factors/metabolism

U2 - 10.1016/j.ydbio.2021.02.008

DO - 10.1016/j.ydbio.2021.02.008

M3 - Article

C2 - 33774010

SN - 0012-1606

VL - 476

SP - 53

EP - 67

JO - Developmental Biology

JF - Developmental Biology

ER -

CREB-binding protein (CBP) gene family regulates planarian survival and stem cell differentiation

Abstract

Keywords

Access to Document

Fingerprint

Cite this