The correlations of the function and positional distribution of the cis-elements CArG around the TSS in the genes of Mus musculus

Genome ◽  
2009 ◽  
Vol 52 (3) ◽  
pp. 217-221 ◽  
Author(s):  
Xia Shen ◽  
Bruce Walsh ◽  
Jing J. Li ◽  
Hong X. Pang ◽  
Wen J. Wang ◽  
...  
Keyword(s):  
Binding Sites ◽  
Copy Number ◽  
Serum Response Factor ◽  
Sequence Data ◽  
Positional Distribution ◽  
Cis Elements ◽  
Transcription Start ◽  
Data Set ◽  
Control Set ◽  
Serum Response

While many studies of cis-elements CArG bound by serum response factor (SRF) are in progress, little is known about the positional distribution of the functional CArG elements around the transcription start site (TSS) of genes that they influence. We use a validated CArG data set to calculate the distance distribution of functional CArG elements around the TSS. Distances between adjacent CArGs were also analyzed. We compare these distributions with those derived using a control set of randomly selected CArGs (that were not experimentally validated for function). Our results show that most functional CArG elements (108 of 152, 71%) exist upstream of the annotated TSS, with copy number increasing as one moves closer to the TSS. Moreover, the average number of the CArG elements in the CArG-containing genes is significantly more than that in the control genes. Our study extends earlier bioinformatic analyses of functional CArG elements and provides an application of comparative sequence data to the identification of transcription factor binding sites.

scholarly journals Serum response factor binding sites differ in three human cell types

2007 ◽  
Vol 17 (2) ◽  
pp. 136-144 ◽  
Author(s):  
S. J. Cooper ◽  
N. D. Trinklein ◽  
L. Nguyen ◽  
R. M. Myers
Keyword(s):  
Human Cell ◽  
Binding Sites ◽  
Serum Response Factor ◽  
Cell Types ◽  
Response Factor ◽  
Factor Binding ◽  
Serum Response

scholarly journals The Elk-1 and Serum Response Factor Binding Sites in the Major Immediate-Early Promoter of Human Cytomegalovirus Are Required for Efficient Viral Replication in Quiescent Cells and Compensate for Inactivation of the NF-κB Sites in Proliferating Cells

2010 ◽  
Vol 84 (9) ◽  
pp. 4481-4493 ◽  
Author(s):  
Patrizia Caposio ◽  
Anna Luganini ◽  
Matteo Bronzini ◽  
Santo Landolfo ◽  
Giorgio Gribaudo
Keyword(s):  
Gene Expression ◽  
Viral Replication ◽  
Binding Sites ◽  
Hcmv Infection ◽  
Serum Response Factor ◽  
Response Factor ◽  
Proliferating Cells ◽  
Quiescent Cells ◽  
Serum Response ◽  
Major Immediate Early Promoter

ABSTRACT The major immediate-early promoter (MIEP) region of human cytomegalovirus (HCMV) plays a critical role in the regulation of lytic and latent infections by integrating multiple signals supplied by the infecting virus, the type and physiological state of the host cell, and its extracellular surroundings. The interaction of cellular transcription factors with their cognate binding sites, which are present at high densities within the enhancer upstream from the MIEP core promoter, regulate the rate of IE gene transcription and thus affect the outcome of HCMV infection. We have shown previously that the NF-κB binding sites within the MIEP enhancer and cellular NF-κB activity induced by HCMV infection are required for efficient MIEP activity and viral replication in quiescent cells (P. Caposio, A. Luganini, G. Hahn, S. Landolfo, and G. Gribaudo, Cell. Microbiol. 9:2040-2054, 2007). We now show that the inactivation of either the Elk-1 or serum response factor (SRF) binding site within the enhancer also reduces MIEP activation and viral replication of recombinant HCMV viruses in quiescent fibroblasts. In these cells, we show that the expression of either Elk-1 or SRF is required for optimal IE gene expression, and that the HCMV-stimulated activation of the MEK1/2-ERK1/2 signaling axis leads to Elk-1 transcriptional competency. Furthermore, the replication kinetics of recombinant viruses in which NF-κB, Elk-1, and SRF binding sites all are inactivated demonstrate that the higher levels of Elk-1 and SRF binding to MIEP in proliferating cells can compensate even for a lack of HCMV-induced NF-κB-mediated MIEP transactivation. These observations highlight the importance of the combination of different MIEP binding sites to optimize IE gene expression in cells in different physiological states.

scholarly journals Increased actin polymerization reduces the inhibition of serum response factor activity by Yin Yang 1

2002 ◽  
Vol 364 (2) ◽  
pp. 547-554 ◽  
Author(s):  
Peter D. ELLIS ◽  
Karen M. MARTIN ◽  
Colin RICKMAN ◽  
James C. METCALFE ◽  
Paul R. KEMP
Keyword(s):  
Binding Sites ◽  
Serum Response Factor ◽  
C2c12 Cells ◽  
Response Factor ◽  
P19 Cells ◽  
Lim Kinase ◽  
Yin Yang 1 ◽  
Yin Yang ◽  
Carg Box ◽  
Serum Response

Recent evidence has implicated CC(A/TrichG)GG (CArG) boxes, binding sites for serum response factor (SRF), in the regulation of expression of a number of genes in response to changes in the actin cytoskeleton. In many cases, the activity of SRF at CArG boxes is modulated by transcription factors binding to overlapping (e.g. Yin Yang 1, YY1) or adjacent (e.g. ets) binding sites. However, the mechanisms by which SRF activity is regulated by the cytoskeleton have not been determined. To investigate these mechanisms, we screened for cells that did or did not increase the activity of a fragment of the promoter for a smooth-muscle (SM)-specific gene SM22α, in response to changes in actin cytoskeletal polymerization induced by LIM kinase. These experiments showed that vascular SM cells (VSMCs) and C2C12 cells increased the activity of promoters containing at least one of the SM22α CArG boxes (CArG near) in response to LIM kinase, whereas P19 cells did not. Bandshift assays using a probe to CArG near showed that P19 cells lacked detectable YY1 DNA binding to the CArG box in contrast with the other two cell types. Expression of YY1 in P19 cells inhibited SM22α promoter activity and conferred responsiveness to LIM kinase. Mutation of the CArG box to inhibit YY1 or SRF binding indicated that both factors were required for the LIM kinase response in VSMCs and C2C12 cells. The data indicate that changes in the actin cytoskeletal organization modify SRF activity at CArG boxes by modulating YY1-dependent inhibition.

scholarly journals Serum Response Factor (SRF) Drives the Transcriptional Upregulation of the MDM4 Oncogene in HCC

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 199
Author(s):  
Rossella Pellegrino ◽  
Abhishek Thavamani ◽  
Diego F. Calvisi ◽  
Jan Budczies ◽  
Ariane Neumann ◽  
...  
Keyword(s):  
Copy Number ◽  
Molecular Mechanisms ◽  
Serum Response Factor ◽  
Liver Tumors ◽  
Luciferase Reporter ◽  
Precision Oncology ◽  
Response Factor ◽  
Murine Liver ◽  
Serum Response

Different molecular mechanisms support the overexpression of the mouse double minute homolog 4 (MDM4), a functional p53 inhibitor, in human hepatocellular carcinoma (HCC). However, the transcription factors (TFs) leading to its transcriptional upregulation remain unknown. Following promoter and gene expression analyses, putative TFs were investigated using gene-specific siRNAs, cDNAs, luciferase reporter assays, chromatin immunoprecipitation, and XI-011 drug treatment in vitro. Additionally, MDM4 expression was investigated in SRF-VP16iHep transgenic mice. We observed a copy-number-independent upregulation of MDM4 in human HCCs. Serum response factor (SRF), ELK1 and ELK4 were identified as TFs activating MDM4 transcription. While SRF was constitutively detected in TF complexes at the MDM4 promoter, presence of ELK1 and ELK4 was cell-type dependent. Furthermore, MDM4 was upregulated in SRF-VP16-driven murine liver tumors. The pharmacological inhibitor XI-011 exhibited anti-MDM4 activity by downregulating the TFs driving MDM4 transcription, which decreased HCC cell viability and increased apoptosis. In conclusion, SRF drives transcriptional MDM4 upregulation in HCC, acting in concert with either ELK1 or ELK4. The transcriptional regulation of MDM4 may be a promising target for precision oncology of human HCC, as XI-011 treatment exerts anti-MDM4 activity independent from the MDM4 copy number and the p53 status.

scholarly journals KLF3 Regulates Muscle-Specific Gene Expression and Synergizes with Serum Response Factor on KLF Binding Sites

2010 ◽  
Vol 30 (14) ◽  
pp. 3430-3443 ◽  
Author(s):  
Charis L. Himeda ◽  
Jeffrey A. Ranish ◽  
Richard C. M. Pearson ◽  
Merlin Crossley ◽  
Stephen D. Hauschka
Keyword(s):  
Binding Sites ◽  
Serum Response Factor ◽  
Control Element ◽  
Specific Gene ◽  
Response Factor ◽  
Gene Promoters ◽  
Muscle Creatine Kinase ◽  
Muscle Genes ◽  
Muscle Gene ◽  
Serum Response

ABSTRACT This study identifies KLF3 as a transcriptional regulator of muscle genes and reveals a novel synergistic interaction between KLF3 and serum response factor (SRF). Using quantitative proteomics, KLF3 was identified as one of several candidate factors that recognize the MPEX control element in the Muscle creatine kinase (MCK) promoter. Chromatin immunoprecipitation analysis indicated that KLF3 is enriched at many muscle gene promoters (MCK, Myosin heavy chain IIa, Six4, Calcium channel receptor α-1, and Skeletal α-actin), and two KLF3 isoforms are upregulated during muscle differentiation. KLF3 and SRF physically associate and synergize in transactivating the MCK promoter independently of SRF binding to CArG motifs. The zinc finger and repression domains of KLF3 plus the MADS box and transcription activation domain of SRF are implicated in this synergy. Our results provide the first evidence of a role for KLF3 in muscle gene regulation and reveal an alternate mechanism for transcriptional regulation by SRF via its recruitment to KLF binding sites. Since both factors are expressed in all muscle lineages, SRF may regulate many striated- and smooth-muscle genes that lack known SRF control elements, thus further expanding the breadth of the emerging CArGome.

scholarly journals Muscle Specificity Encoded by Specific Serum Response Factor-binding Sites

2001 ◽  
Vol 276 (20) ◽  
pp. 17206-17212 ◽  
Author(s):  
Priscilla S. Chang ◽  
Li Li ◽  
John McAnally ◽  
Eric N. Olson
Keyword(s):  
Binding Sites ◽  
Serum Response Factor ◽  
Response Factor ◽  
Factor Binding ◽  
Specific Serum ◽  
Serum Response ◽  
Muscle Specificity

scholarly journals Post-transcriptional regulation of MRTF-A by miRNAs during myogenic differentiation of myoblasts

2020 ◽  
Vol 48 (16) ◽  
pp. 8927-8942
Author(s):  
Ingo Holstein ◽  
Anurag Kumar Singh ◽  
Falk Pohl ◽  
Danny Misiak ◽  
Juliane Braun ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Mirna Expression ◽  
Binding Sites ◽  
Serum Response Factor ◽  
Myogenic Differentiation ◽  
Affinity Purification ◽  
Protein Abundance ◽  
Related Transcription Factor ◽  
Post Transcriptional Regulation ◽  
Serum Response

Abstract The differentiation and regeneration of skeletal muscle from myoblasts to myotubes involves myogenic transcription factors, such as myocardin-related transcription factor A (MRTF-A) and serum response factor (SRF). In addition, post-transcriptional regulation by miRNAs is required during myogenesis. Here, we provide evidence for novel mechanisms regulating MRTF-A during myogenic differentiation. Endogenous MRTF-A protein abundance and activity decreased during C2C12 differentiation, which was attributable to miRNA-directed inhibition. Conversely, overexpression of MRTF-A impaired differentiation and myosin expression. Applying miRNA trapping by RNA affinity purification (miTRAP), we identified miRNAs which directly regulate MRTF-A via its 3′UTR, including miR-1a-3p, miR-206-3p, miR-24-3p and miR-486-5p. These miRNAs were upregulated during differentiation and specifically recruited to the 3′UTR of MRTF-A. Concomitantly, Ago2 recruitment to the MRTF-A 3′UTR was considerably increased, whereas Dicer1 depletion or 3′UTR deletion elevated MRTF-A and inhibited differentiation. MRTF-A protein expression was inhibited by ectopic miRNA expression in murine C2C12 and primary human myoblasts. 3′UTR reporter activity diminished upon differentiation or miRNA expression, whereas deletion of the predicted binding sites reversed these effects. Furthermore, TGF-β abolished MRTF-A reduction and decreased miR-486-5p expression. Our findings implicate miR-24-3p and miR-486-5p in the repression of MRTF-A and suggest a complex network of transcriptional and post-transcriptional mechanisms regulating myogenesis.

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