Abstract:
:Over 400 Krüppel-associated box zinc finger proteins (KRAB-ZFPs) are encoded in mammalian genomes. While KRAB-ZFPs strongly repress transcription in vitro, little is known about their biological function or gene targets in vivo. Regulator of sex limitation 1 (Rsl1), one of the first KRAB-Zfp genes assigned a physiological role, accentuates sex-biased liver gene expression, most dramatically for mouse sex-limited protein (Slp), which provides an in vivo reporter of KRAB-ZFP function. Slp is induced in males in the liver and kidney by growth hormone (GH) and androgen, respectively. In the liver but not kidney, the Rsl1 genotype correlates with methylation of a CpG dinucleotide in the Slp promoter that is demethylated at puberty. RSL1 binds 2 kb upstream of the Slp promoter, both in vitro and in vivo, within an enhancer containing response elements for STAT5b. Chromatin immunoprecipitation (ChIP) assays demonstrate that RSL1 recruits KAP1/TRIM28, the corepressor for KRAB action in vitro, to this enhancer. Slp induction requires rapid cycling of STAT5b in chromatin. Remarkably, RSL1 simultaneously binds adjacent to STAT5b with a reciprocal binding pattern that limits hormonal response. These experiments demonstrate a surprisingly dynamic interplay between a hormonal activator, STAT5b, and a KRAB-ZFP repressor and provide unique insights into KRAB-ZFP epigenetic mechanisms.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Krebs CJ,Schultz DC,Robins DMdoi
10.1128/MCB.00615-12subject
Has Abstractpub_date
2012-09-01 00:00:00pages
3732-42issue
18eissn
0270-7306issn
1098-5549pii
MCB.00615-12journal_volume
32pub_type
杂志文章abstract::Calcineurin (Cn) is a calcium-activated serine/threonine protein phosphatase that is broadly implicated in diverse cellular processes, including the regulation of gene expression. During skeletal muscle differentiation, Cn activates the nuclear factor of activated T-cell (NFAT) transcription factor but also promotes d...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00063-19
更新日期:2019-09-11 00:00:00
abstract::Protein ubiquitination provides an efficient and reversible mechanism to regulate cell cycle progression and checkpoint control. Numerous regulatory proteins direct the addition of ubiquitin to lysine residues on target proteins, and these are countered by an army of deubiquitinating enzymes (DUBs). BRCA1-associated p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01517-08
更新日期:2009-04-01 00:00:00
abstract::Hes1 is a mammalian basic helix-loop-helix transcriptional repressor that inhibits neuronal differentiation together with corepressors of the Groucho (Gro)/Transducin-like Enhancer of split (TLE) family. The interaction of Hes1 with Gro/TLE is mediated by a WRPW tetrapeptide present in all Hairy/Enhancer of split (Hes...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.19.6922-6935.2003
更新日期:2003-10-01 00:00:00
abstract::We have identified stable transcripts from the so-called nontranscribed spacer region (NTS) of the nuclear ribosomal DNA repeat in certain respiration-deficient strains of Saccharomyces cerevisiae. These RNAs, which are transcribed from the same strand as is the 37S rRNA precursor, are 500 to 800 nucleotides long and ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.5.1897
更新日期:1989-05-01 00:00:00
abstract::Inactivation of the TATA-binding protein-containing complex TFIIIB contributes to the mitotic repression of RNA polymerase III transcription, both in frogs and in humans (J. M. Gottesfeld, V. J. Wolf, T. Dang, D. J. Forbes, and P. Hartl, Science 263:81-84, 1994; R. J. White, T. M. Gottlieb, C. S. Downes, and S. P. Jac...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.12.6653
更新日期:1995-12-01 00:00:00
abstract::The 12p13 ETV6 (TEL) gene is frequently targeted by chromosomal translocations in human malignancies, resulting in the formation of oncogenic ETV6 gene fusions. Many of the known partner genes encode protein tyrosine kinases (PTKs), generating fusion proteins that function as chimeric PTKs. ETV6-NTRK3 (EN), comprised ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.11.4636-4650.2004
更新日期:2004-06-01 00:00:00
abstract::An ssu72 mutant of Saccharomyces cerevisiae was identified as an enhancer of a TFIIB defect (sua7-1) that confers both a cold-sensitive growth defect and a downstream shift in transcription start site selection. The ssu72-1 allele did not affect cold sensitivity but, in combination with sua7-1, created a heat-sensitiv...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.4.1557
更新日期:1996-04-01 00:00:00
abstract::A prominent hallmark of most human cancer is aneuploidy, which is a result of the chromosomal instability of cancer cells and is thought to contribute to the initiation and progression of most carcinomas. The developmentally regulated GATA6 transcription factor is commonly lost in ovarian cancer, and the loss of its e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00087-09
更新日期:2009-09-01 00:00:00
abstract::The human immunodeficiency virus type 1 (HIV-1) Tat protein activates transcription elongation by stimulating the Tat-activated kinase (TAK/p-TEFb), a protein kinase composed of CDK9 and its cyclin partner, cyclin T1. CDK9 is able to hyperphosphorylate the carboxyl-terminal domain (CTD) of the large subunit of RNA pol...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.4.1079-1093.2002
更新日期:2002-02-01 00:00:00
abstract::Loss of p53 sensitizes to antimicrotubule agents in human tumor cells, but little is known about its role during mitosis. We have identified the Polo-like kinase family member serum inducible kinase (Snk/Plk2) as a novel p53 target gene. Snk/Plk2 mutagenesis demonstrated that its kinase activity is negatively regulate...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.16.5556-5571.2003
更新日期:2003-08-01 00:00:00
abstract::Telomeres are essential for protecting the ends of chromosomes and preventing chromosome fusion. Telomere loss has been proposed to play an important role in the chromosomal rearrangements associated with tumorigenesis. To determine the relationship between telomere loss and chromosome instability in mammalian cells, ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.13.4836-4850.2002
更新日期:2002-07-01 00:00:00
abstract::The Csk tyrosine kinase negatively regulates the Src family kinases Lck and Fyn in T cells. Engagement of the T-cell antigen receptor results in a removal of Csk from the lipid raft-associated transmembrane protein PAG/Cbp. Instead, Csk becomes associated with an approximately 72-kDa tyrosine-phosphorylated protein, w...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.6.2227-2241.2005
更新日期:2005-03-01 00:00:00
abstract::To investigate in vivo roles of a murine hypothalamic homeobox gene, Bsx, we generated and analyzed two mutant alleles, Bsx(DeltaHD) and Bsx(lacZ). Bsx(DeltaHD) lacks the homeodomain, and Bsx(lacZ) is an insertion of a lacZ reporter gene. Bsx-lacZ expression was detected in the hypothalamus and pineal gland and reiter...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00215-07
更新日期:2007-07-01 00:00:00
abstract::NF-kappaB2 (p100/p52), a member of the NF-kappaB/Rel family of transcription factors, is involved in the regulation of a variety of genes important for immune function. Previously, we have shown that the NF-kappaB2 gene is regulated in a positive and a negative manner. Two kappaB elements within the NF-kappaB2 promote...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.4.2077
更新日期:1998-04-01 00:00:00
abstract::Toxoplasma gondii is an obligate intracellular pathogen within the phylum Apicomplexa. Invasion and egress by this protozoan parasite are rapid events that are dependent upon parasite motility and appear to be directed by fluctuations in intracellular [Ca(2+)]. Treatment of infected host cells with the calcium ionopho...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.24.9399-9408.2000
更新日期:2000-12-01 00:00:00
abstract::We have identified an essential cis element in the proximal promoter region of the rat carbamyl phosphate synthetase I (CPSI) gene that is requisite for promoter activity in liver nuclear extracts. Excess synthetic oligonucleotides specifying this region abolished promoter-dependent in vitro transcription. We show tha...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.7.2928
更新日期:1989-07-01 00:00:00
abstract::Moloney murine sarcoma virus carries an oncogenic sequence (v-mos) which is homologous to a single copy gene (c-mos) present in the normal cells of several vertebrate species. Because of the possible significance of c-mos sequences in normal development and malignant transformation induced by physical or chemical agen...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.2.1.42
更新日期:1982-01-01 00:00:00
abstract::The activation of Raf kinases by the small GTPase Ras requires two major sets of phosphorylations. One set lies within the activation loop, and the other lies within the N-terminal acidic region (N region). In the most abundant isoform of Raf, C-Raf, N-region phosphorylations occur on serine 338 (S338) and tyrosine 34...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00132-17
更新日期:2017-09-12 00:00:00
abstract::To interrogate endogenous p21(WAF1/CIP1) (p21) promoter activity under basal conditions and in response to various forms of stress, knock-in imaging reporter mice in which expression of firefly luciferase (FLuc) was placed under the control of the endogenous p21 promoter within the Cdkn1a gene locus were generated. Bi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.05243-11
更新日期:2011-09-01 00:00:00
abstract::Transcription factor CREB regulates cyclic AMP (cAMP)-dependent gene expression by binding to and activating transcription from cAMP response elements (CREs) in the promoters of target genes. The transcriptional transactivation functions of CREB are activated by its phosphorylation by cAMP-dependent protein kinase A (...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.1.415
更新日期:1995-01-01 00:00:00
abstract::There are nearly 50 forkhead (FOX) transcription factors encoded in the human genome and, due to sharing a common DNA binding domain, they are all thought to bind to similar DNA sequences. It is therefore unclear how these transcription factors are targeted to specific chromatin regions to elicit specific biological e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00881-12
更新日期:2013-01-01 00:00:00
abstract::Nonsense-mediated RNA decay (NMD) is an mRNA surveillance mechanism which rapidly degrades select cytoplasmic mRNAs. We and others have shown that NMD is a dynamically regulated process inhibited by amino acid deprivation, hypoxia, and other cellular stresses commonly generated by the tumor microenvironment. This inhi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00174-13
更新日期:2013-06-01 00:00:00
abstract::Expression of the Cyp 2d-9 (steroid 16 alpha-hydroxylase) gene in mouse liver is male specific in such Mus musculus domesticus strains as FVB/N, whereas the corresponding P450 genes in the wild mouse species Mus spretus are not sex specific in their expression. These parental differences in the gene expressions were i...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.8.4158
更新日期:1995-08-01 00:00:00
abstract::Densely methylated DNA sequence islands, designated DMIs, have been observed in two Chinese hamster cell chromosomal replication origins by using a PCR-based chemical method of detection. One of the origins, oriS14, is located within or adjacent to the coding sequence for ribosomal protein S14 on chromosome 2q, and th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.9.5636
更新日期:1994-09-01 00:00:00
abstract::We have cloned CDC9, the structural gene for Saccharomyces cerevisiae DNA ligase, and investigated its transcriptional regulation both as a function of cell cycle stage and after UV irradiation. The steady-state level of DNA ligase mRNA increases at least fourfold in late G1, after the completion of start but before S...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.1.226
更新日期:1985-01-01 00:00:00
abstract::The connections between various nuclear processes and specific histone posttranslational modifications are dependent to a large extent on the acquisition of those modifications after histone synthesis. The reestablishment of histone posttranslational modifications after S phase is especially critical for H3K9 and H3K2...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.06673-11
更新日期:2012-07-01 00:00:00
abstract::Cells of the human embryonal carcinoma line NEC14 proliferate as densely packed clusters consisting of small, polygonal stem cells and do not express a detectable level of fibronectin (FN). Upon induction of differentiation by treatment with N,N'-hexamethylene bisacetamide (HMBA), the level of FN mRNA increased steepl...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.5.3010
更新日期:1998-05-01 00:00:00
abstract::Myocyte enhancer factor 2 (MEF2) transcription factors cooperate with the MyoD family of basic helix-loop-helix (bHLH) transcription factors to drive skeletal muscle development during embryogenesis, but little is known about the potential functions of MEF2 factors in postnatal skeletal muscle. Here we show that skele...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01187-07
更新日期:2007-12-01 00:00:00
abstract::ICP4 of herpes simplex virus is responsible for the activation of viral transcription during infection. It also efficiently activates and represses transcription in vitro depending on the promoter context. The contacts made between ICP4 and the cellular proteins that result in activated transcription have not been ide...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.6.3085
更新日期:1996-06-01 00:00:00
abstract::We isolated the gene for citrate synthase (citrate oxaloacetate lyase; EC 4.1.3.7) from Saccharomyces cerevisiae and ablated it by inserting the yeast LEU2 gene within its reading frame. This revealed a second, nonmitochondrial citrate synthase. Like the mitochondrial enzyme, this enzyme was sensitive to glucose repre...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.2.488
更新日期:1986-02-01 00:00:00