Abstract:
:The Sry-related high-mobility-group box transcription factor Sox9 recruits the redundant L-Sox5 and Sox6 proteins to effect chondrogenesis, but the mode of action of the trio remains unclear. We identify here a highly conserved 359-bp sequence 10 kb upstream of the Agc1 gene for aggrecan, a most essential cartilage proteoglycan and key marker of chondrocyte differentiation. This sequence directs expression of a minimal promoter in both embryonic and adult cartilage in transgenic mice, in a manner that matches Agc1 expression. The chondrogenic trio is required and sufficient to mediate the activity of this enhancer. It acts directly, Sox9 binding to a critical cis-acting element and L-Sox5/Sox6 binding to three additional elements, which are cooperatively needed. Upon binding to their specific sites, L-Sox5/Sox6 increases the efficiency of Sox9 binding to its own recognition site and thereby robustly potentiates the ability of Sox9 to activate the enhancer. L-Sox5/Sox6 similarly secures Sox9 binding to Col2a1 (encoding collagen-2) and other cartilage-specific enhancers. This study thus uncovers critical cis-acting elements and transcription factors driving Agc1 expression in cartilage and increases understanding of the mode of action of the chondrogenic Sox trio.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Han Y,Lefebvre Vdoi
10.1128/MCB.00695-08subject
Has Abstractpub_date
2008-08-01 00:00:00pages
4999-5013issue
16eissn
0270-7306issn
1098-5549pii
MCB.00695-08journal_volume
28pub_type
杂志文章abstract::Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) strongly inhibit transcriptional activation mediated by nuclear hormone receptors, including hepatocyte nuclear factor 4 (HNF-4). COUP-TFs repress HNF-4-dependent gene expression by competition with HNF-4 for common binding sites found in several reg...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.5.2790
更新日期:1997-05-01 00:00:00
abstract::The NK-2 homeobox genes have been shown to play critical roles in the development of specific organs and tissues. Nkx2.6 is a member of the NK-2 homeobox gene family and is most closely related to the Drosophila tinman gene. Nkx2.6 is expressed in the caudal pharyngeal pouches, the caudal heart progenitors, the sinus ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.8.2874-2879.2000
更新日期:2000-04-01 00:00:00
abstract::Rad53 of Saccharomyces cerevisiae is a checkpoint kinase whose structure and function are conserved among eukaryotes. When a cell detects damaged DNA, Rad53 activity is dramatically increased, which ultimately leads to changes in DNA replication, repair, and cell division. Despite its central role in checkpoint signal...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.10.3405-3416.2003
更新日期:2003-05-01 00:00:00
abstract::Nuclear factor kappa B (NF-kappa B) is a ubiquitous transcription factor which binds to decameric DNA sequences (kappa B sites) and regulates transcription of multiple genes. The activity of NF-kappa B is regulated by an inhibitor protein, I kappa B, which sequesters NF-kappa B in the cytoplasm. Release of I kappa B a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.5.3276
更新日期:1994-05-01 00:00:00
abstract::A gene assigned to human chromosome 1q32-41 encodes a novel protein of 3,113 amino acids containing an internal tandem repeat of 177 amino acids. The protein, which we have named "mitosin," was identified by direct binding to purified retinoblastoma protein in vitro with a region distantly related to the retinoblastom...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.9.5017
更新日期:1995-09-01 00:00:00
abstract::We analyzed the binding site(s) for Grb2 on the epidermal growth factor (EGF) receptor (EGFR), using cell lines overexpressing EGFRs containing various point and deletion mutations in the carboxy-terminal tail. Results of co-immunoprecipitation experiments suggest that phosphotyrosines Y-1068 and Y-1173 mediate the bi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.8.5192
更新日期:1994-08-01 00:00:00
abstract::T-lymphocyte stimulation requires activation of several protein kinases, including the major phorbol ester receptor protein kinase C (PKC), ultimately leading to induction of lymphokines, such as interleukin-2 (IL-2). The revelant PKC isoforms which are involved in the activation cascades of nuclear transcription fact...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.4.1842
更新日期:1996-04-01 00:00:00
abstract::Using in vitro replication assays, we compared native with salt-treated simian virus 40 minichromosomes isolated from infected cell nuclei. Minichromosomes from both preparations contain the full complement of nucleosomes, but salt treatment removes histone H1 and a fraction of nonhistone chromatin proteins. Both type...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.2.1059
更新日期:1993-02-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.8.2653
更新日期:1987-08-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.8.5558
更新日期:1994-08-01 00:00:00
abstract::Mediator is a general coactivator complex connecting transcription activators and RNA polymerase II. Recent work has shown that the nuclear receptor-interacting MED1/TRAP220 subunit of Mediator is required for peroxisome proliferator-activated receptor gamma (PPARgamma)-stimulated adipogenesis of mouse embryonic fibro...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00967-07
更新日期:2008-02-01 00:00:00
abstract::We set up an alternative splicing system in vitro in which the relative amounts of two spliced RNAs, one containing and the other lacking a particular exon, were directly proportional to the length of an inverted repeat inserted into the flanking introns. We then used the system to measure the effect of intramolecular...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.9.3194
更新日期:1987-09-01 00:00:00
abstract::Heteroduplexes formed between DNA strands derived from different homologous chromosomes are an intermediate in meiotic crossing over in the yeast Saccharomyces cerevisiae and other eucaryotes. A heteroduplex formed between wild-type and mutant genes will contain a base pair mismatch; failure to repair this mismatch wi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.2.737
更新日期:1991-02-01 00:00:00
abstract::We have analyzed the effects of transformation by Rous sarcoma virus on expression of types I and II collagen and fibronectin genes in vertebral chondrocytes and compared them with expression of these genes in skin fibroblasts. Transformed chondrocytes display a dramatically decreased amount of type II collagen RNA, w...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.5.1002
更新日期:1985-05-01 00:00:00
abstract::Cell adhesion and spreading depend on activation of mitogen-activated kinase, which in turn is regulated both by growth factor and integrin signaling. Growth factors, such as epidermal growth factor, are capable of activating Ras and Raf, but integrin signaling is required to couple Raf to MEK and MEK to extracellular...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.6.2308-2317.2004
更新日期:2004-03-01 00:00:00
abstract::Transcription activation of alpha-specific genes in Saccharomyces cerevisiae is regulated by two proteins, MCM1 and alpha 1, which bind to DNA sequences, called P'Q elements, found upstream of alpha-specific genes. Neither MCM1 nor alpha 1 alone binds efficiently to P'Q elements. Together, however, they bind cooperati...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.11.6866
更新日期:1993-11-01 00:00:00
abstract::DHTKD1, a part of 2-ketoadipic acid dehydrogenase complex, is involved in lysine and tryptophan catabolism. Mutations in DHTKD1 block the metabolic pathway and cause 2-aminoadipic and 2-oxoadipic aciduria (AMOXAD), an autosomal recessive inborn metabolic disorder. In addition, a nonsense mutation in DHTKD1 that we ide...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00085-18
更新日期:2018-06-14 00:00:00
abstract::The interleukin-2 receptor (IL-2R) beta chain (IL-2R beta) is an essential signaling component of high- and intermediate-affinity IL-2Rs. Our laboratory previously reported that a DNA fragment containing 857 bp of 5'-flanking sequence of the human IL-2R beta gene exhibited promoter activity. We have now further charac...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.10.6201
更新日期:1993-10-01 00:00:00
abstract::To determine the types of alterations in gene structure induced by DNA-alkylating agents, we analyzed the restriction enzyme cleavage patterns of adenine phosphoribosyltransferase gene sequences in mutant strains of Chinese hamster ovary cells deficient in this enzyme. Base pair changes as detected by loss of restrict...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.2.11.1459
更新日期:1982-11-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.16.6964-6979.2005
更新日期:2005-08-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2014-11-15 00:00:00
abstract::Hybridization to synthetic oligonucleotides representing conserved regions in the promoter and first intron of several vertebrate beta-actin genes was used to discriminate between what appears to be a single functional beta-actin gene and numerous pseudogenes in the mouse genome. Sequences derived from the 5' end of t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.1.480
更新日期:1988-01-01 00:00:00
abstract::Hepatocyte nuclear factor 4α (HNF4α) is a critical factor for hepatocyte differentiation. HNF4α expression is decreased in hepatocellular carcinoma (HCC), which suggests a role in repression of hepatocyte dedifferentiation. In the present study, hepatic expression of HNF4γ was increased in liver-specific Hnf4a-null mi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00213-18
更新日期:2018-11-28 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00744-15
更新日期:2016-01-25 00:00:00
abstract::In yeast there are at least 14 members of the beta-karyopherin protein family that govern the movement of a diverse set of cargoes between the nucleus and cytoplasm. Knowledge of the cargoes carried by each karyopherin and insight into the mechanisms of transport are fundamental to understanding constitutive and regul...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.19.8487-8503.2004
更新日期:2004-10-01 00:00:00
abstract::The scid mouse mutation affects V(D)J rearrangement and double-strand break repair. scid V(D)J rearrangement is characterized by defective coding joint formation which prevents the development of mature B and T cells. Hairpin DNA has been implicated in the formation of V(D)J coding joints. We found scid cells to be pr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.6.3876
更新日期:1994-06-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.9.3582
更新日期:1988-09-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2001-12-01 00:00:00
abstract::To determine the role of poly(A) polymerase in 3'-end processing of mRNA, the effect of purified poly(A) polymerase antibodies on endonucleolytic cleavage and polyadenylation was studied in HeLa nuclear extracts, using adenovirus L3 pre-mRNA as the substrate. Both Mg2+- and Mn2+-dependent reactions catalyzing addition...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.4.1435
更新日期:1989-04-01 00:00:00
abstract::The E2F1, -2, and -3 transcription factors are key downstream targets of the retinoblastoma protein (pRB) tumor suppressor that drive expression of proliferation-associated genes. Here we use mutant mouse strains to investigate E2F3's role in vivo. We show that E2F3 is essential for embryonic viability in the pure 129...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.8.2663-2672.2002
更新日期:2002-04-01 00:00:00