scholarly journals The Transcription Factor HAND1 Is Involved in Cortical Bone Mass through the Regulation of Collagen Expression

2020 ◽  
Vol 21 (22) ◽  
pp. 8638
Author(s):  
Noriko Funato ◽  
Yuki Taga ◽  
Lindsay E. Laurie ◽  
Chisa Tometsuka ◽  
Masashi Kusubata ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Postnatal Development ◽  
Bone Size ◽  
Type I ◽  
Long Bones ◽  
Collagen Expression ◽  
Helix Loop Helix ◽  
Size And Morphology ◽  
Cortical Bone Mass

Temporal and/or spatial alteration of collagen family gene expression results in bone defects. However, how collagen expression controls bone size remains largely unknown. The basic helix-loop-helix transcription factor HAND1 is expressed in developing long bones and is involved in their morphogenesis. To understand the functional role of HAND1 and collagen in the postnatal development of long bones, we overexpressed Hand1 in the osteochondroprogenitors of model mice and found that the bone volumes of cortical bones decreased in Hand1Tg/+;Twist2-Cre mice. Continuous Hand1 expression downregulated the gene expression of type I, V, and XI collagen in the diaphyses of long bones and was associated with decreased expression of Runx2 and Sp7/Osterix, encoding transcription factors involved in the transactivation of fibril-forming collagen genes. Members of the microRNA-196 family, which target the 3′ untranslated regions of COL1A1 and COL1A2, were significantly upregulated in Hand1Tg/+;Twist2-Cre mice. Mass spectrometry revealed that the expression ratios of alpha 1(XI), alpha 2(XI), and alpha 2(V) in the diaphysis increased during postnatal development in wild-type mice, which was delayed in Hand1Tg/+;Twist2-Cre mice. Our results demonstrate that HAND1 regulates bone size and morphology through osteochondroprogenitors, at least partially by suppressing postnatal expression of collagen fibrils in the cortical bones.

scholarly journals An activation domain of the helix-loop-helix transcription factor E2A shows cell type preference in vivo in microinjected zebra fish embryos.

1996 ◽  
Vol 16 (4) ◽  
pp. 1714-1721 ◽  
Author(s):  
F Argenton ◽  
Y Arava ◽  
A Aronheim ◽  
M D Walker
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Transcription Factor ◽  
Transcription Activation ◽  
Cell Types ◽  
Zebra Fish ◽  
Reporter Plasmid ◽  
Activation Domains ◽  
Helix Loop Helix

The E2A protein is a mammalian transcription factor of the helix-loop-helix family which is implicated in cell-specific gene expression in several cell lineages. Mouse E2A contains two independent transcription activation domains, ADI and ADII; whereas ADI functions effectively in a variety of cultured cell lines, ADII shows preferential activity in pancreatic beta cells. To analyze this preferential activity in an in vivo setting, we adapted a system involving transient gene expression in microinjected zebra fish embryos. Fertilized one- to four-cell embryos were coinjected with an expression plasmid and a reporter plasmid. The expression plasmids used encode the yeast Gal4 DNA-binding domain (DBD) alone, or Gal4 DBD fused to ADI, ADII, or VP16. The reporter plasmid includes the luciferase gene linked to a promoter containing repeats of UASg, the Gal4-binding site. Embryo extracts prepared 24 h after injection showed significant luciferase activity in response to each of the three activation domains. To determine the cell types in which the activation domains were functioning, a reporter plasmid encoding beta-galactosidase and then in situ staining of whole embryos were used. Expression of ADI led to activation in all major groups of cell types of the embryo (skin, sclerotome, myotome, notochord, and nervous system). On the other hand, ADII led to negligible expression in the sclerotome, notochord, and nervous system and much more frequent expression in the myotome. Parallel experiments conducted with transfected mammalian cells have confirmed that ADII shows significant activity in myoblast cells but little or no activity in neuronal precursor cells, consistent with our observations in zebra fish. This transient-expression approach permits rapid in vivo analysis of the properties of transcription activation domains: the data show that ADII functions preferentially in cells of muscle lineage, consistent with the notion that certain activation domains contribute to selective gene activation in vivo.

Distribution of type I and type II collagen gene expression during the development of human long bones

Bone ◽  
1990 ◽  
Vol 11 (4) ◽  
pp. 275-279 ◽  
Author(s):  
S. Mundlos ◽  
H. Engel ◽  
I. Michel-Behnke ◽  
B. Zabel
Keyword(s):  
Gene Expression ◽  
Type Ii Collagen ◽  
Type I ◽  
Collagen Gene ◽  
Long Bones ◽  
Type Ii ◽  
Collagen Gene Expression

scholarly journals Molecular and Cellular Function of Transcription Factor 4 in Pitt-Hopkins Syndrome

2021 ◽  
pp. 1-9
Author(s):  
Huei-Ying Chen ◽  
Joseph F. Bohlen ◽  
Brady J. Maher
Keyword(s):  
Transcription Factor ◽  
Regulatory Networks ◽  
Autosomal Dominant ◽  
Autism Spectrum ◽  
Therapeutic Interventions ◽  
Type I ◽  
Helix Loop Helix ◽  
Transcription Factor 4

Transcription factor 4 (TCF4, also known as ITF2 or E2-2) is a type I basic helix-loop-helix transcription factor. Autosomal dominant mutations in TCF4 cause Pitt-Hopkins syndrome (PTHS), a rare syndromic form of autism spectrum disorder. In this review, we provide an update on the progress regarding our understanding of TCF4 function at the molecular, cellular, physiological, and behavioral levels with a focus on phenotypes and therapeutic interventions. We examine upstream and downstream regulatory networks associated with TCF4 and discuss a range of in vitro and in vivo data with the aim of understanding emerging TCF4-specific mechanisms relevant for disease pathophysiology. In conclusion, we provide comments about exciting future avenues of research that may provide insights into potential new therapeutic targets for PTHS.

scholarly journals Profiling transcription factor sub-networks in type I interferon signaling and in response to SARS-CoV-2 infection

2021 ◽  
Author(s):  
Chilakamarti V. Ramana
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Immune Modulation ◽  
Type I Interferon ◽  
Lung Epithelial Cells ◽  
Type I ◽  
Interferon Signaling ◽  
Lung Epithelial

AbstractType I interferons (IFN α/β) play a central role in innate immunity to respiratory viruses, including coronaviruses. Genetic defects in type I interferon signaling were reported in a significant proportion of critically ill CoOVID-19 patients. Extensive studies on interferon-induced intracellular signal transduction pathways led to the elucidation of the Jak-Stat pathway. Furthermore, advances in gene expression profiling by microarrays have revealed that type I interferon rapidly induced multiple transcription factor mRNA levels. In this study, transcription factor profiling in the transcriptome was used to gain novel insights into the role of inducible transcription factors in response to type I interferon signaling in immune cells and in lung epithelial cells after SARS-CoV-2 infection. Modeling the interferon-inducible transcription factor mRNA data in terms of distinct sub-networks based on biological functions such as antiviral response, immune modulation, and cell growth revealed enrichment of specific transcription factors in mouse and human immune cells. The evolutionarily conserved core type I interferon gene expression consists of the inducible transcriptional factor mRNA of the antiviral response sub-network and enriched in granulocytes. Analysis of the type I interferon-inducible transcription factor sub-networks as distinct protein-protein interaction pathways revealed insights into the role of critical hubs in signaling. Interrogation of multiple microarray datasets revealed that SARS-CoV-2 induced high levels of IFN-beta and interferon-inducible transcription factor mRNA in human lung epithelial cells. Transcription factor mRNA of the three major sub-networks regulating antiviral, immune modulation, and cell growth were differentially regulated in human lung epithelial cell lines after SARS-CoV-2 infection and in the tissue samples of COVID-19 patients. A subset of type I interferon-inducible transcription factors and inflammatory mediators were specifically enriched in the lungs and neutrophils of Covid-19 patients. The emerging complex picture of type I IFN transcriptional regulation consists of a rapid transcriptional switch mediated by the Jak-Stat cascade and a graded output of the inducible transcription factor activation that enables temporal regulation of gene expression.

scholarly journals Homeostatic and Interferon-induced gene expression represent different states of promoter-associated transcription factor ISGF3

2018 ◽  
Author(s):  
Ekaterini Platanitis ◽  
Duygu Demiroz ◽  
Christophe Capelle ◽  
Anja Schneller ◽  
Markus Hartl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Resting State ◽  
Living Cells ◽  
Type I ◽  
Basal Expression ◽  
Proteomic Approach ◽  
Signalling Cascades ◽  
Induced Genes ◽  
Stat Pathway

AbstractCells maintain the balance between homeostasis and inflammation by adapting and integrating the activity of intracellular signalling cascades, including the JAK-STAT pathway. Our understanding how a tailored switch from homeostasis to a strong receptor-dependent response is coordinated remains limited. We used an integrated transcriptomic and proteomic approach to analyze transcription-factor binding, gene expression and in vivo proximity-dependent labelling of proteins in living cells under homeostatic and interferon (IFN)-induced conditions. We show that interferons (IFN) switch murine macrophages from resting-state to induced gene expression by alternating subunits of transcription factor ISGF3. Whereas preformed STAT2-IRF9 complexes control basal expression of IFN-induced genes (ISG), both type I IFN and, unexpectedly, IFNγ cause promoter binding of a complete ISGF3 complex containing STAT1, STAT2 and IRF9. In contrast to the dogmatic view of ISGF3 formation in the cytoplasm, our results suggest a model wherein the assembly of the ISGF3 complex occurs on DNA.

scholarly journals Myocardin-related Transcription Factor-A Complexes Activate Type I Collagen Expression in Lung Fibroblasts

2011 ◽  
Vol 286 (51) ◽  
pp. 44116-44125 ◽  
Author(s):  
Larry L. Luchsinger ◽  
Cassandra A. Patenaude ◽  
Barbara D. Smith ◽  
Matthew D. Layne
Keyword(s):  
Transcription Factor ◽  
Type I Collagen ◽  
Lung Fibroblasts ◽  
Type I ◽  
Collagen Expression ◽  
Related Transcription Factor
Sign in / Sign up

Export Citation Format

Share Document