|Replacement Information||06-574 is a recommended replacement for CBL770|
Key Spec Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|H, M||IF, IHC, IP, WB, ChIP||M||Ascites||Monoclonal Antibody|
|Presentation||Mouse monoclonal in buffer containing 0.05% sodium azide and 30% glycerol.|
|Safety Information according to GHS|
|Material Size||100 µL|
|Anti-LSD1/BHC110 - 2039870||2039870|
|Anti-LSD1/BHC110 - 2276335||2276335|
|Anti-LSD1/BHC110 - 30522||30522|
|Anti-LSD1/BHC110 - 33455||33455|
|Anti-LSD1/BHC110 - JBC1361937||JBC1361937|
|Anti-LSD1/BHC110 - NG1904282||NG1904282|
|Anti-LSD1/BHC110 Monoclonal Antibody||2890801|
|Reference overview||Application||Pub Med ID|
|Lysine-specific histone demethylase 1 inhibitors control breast cancer proliferation in ERα-dependent and -independent manners.|
Pollock, JA; Larrea, MD; Jasper, JS; McDonnell, DP; McCafferty, DG
ACS chemical biology 7 1221-31 2012
Lysine specific demethylase 1 (LSD1, also known as KDM1) is a histone modifying enzyme that regulates the expression of many genes important in cancer progression and proliferation. It is present in various transcriptional complexes including those containing the estrogen receptor (ER). Indeed, inhibition of LSD1 activity and or expression has been shown to attenuate estrogen signaling in breast cancer cells in vitro, implicating this protein in the pathogenesis of cancer. Herein we describe experiments that utilize small molecule inhibitors, phenylcyclopropylamines, along with small interfering RNA to probe the role of LSD1 in breast cancer proliferation and in estrogen-dependent gene transcription. Surprisingly, whereas we have confirmed that inhibition of LSD1 strongly inhibits proliferation of breast cancer cells, we have determined that the cytostatic actions of LSD1 inhibition are not impacted by ER status. These data suggest that LSD1 may be a useful therapeutic target in several types of breast cancer; most notably, inhibitors of LSD1 may have utility in the treatment of ER-negative cancers for which there are minimal therapeutic options.
|Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that coexist on the lysine tail.|
Brasacchio, D; Okabe, J; Tikellis, C; Balcerczyk, A; George, P; Baker, EK; Calkin, AC; Brownlee, M; Cooper, ME; El-Osta, A
Diabetes 58 1229-36 2009
Results from the Diabetes Control Complications Trial (DCCT) and the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) Study and more recently from the U.K. Prospective Diabetes Study (UKPDS) have revealed that the deleterious end-organ effects that occurred in both conventional and more aggressively treated subjects continued to operate greater than 5 years after the patients had returned to usual glycemic control and is interpreted as a legacy of past glycemia known as "hyperglycemic memory." We have hypothesized that transient hyperglycemia mediates persistent gene-activating events attributed to changes in epigenetic information.Models of transient hyperglycemia were used to link NFkappaB-p65 gene expression with H3K4 and H3K9 modifications mediated by the histone methyltransferases (Set7 and SuV39h1) and the lysine-specific demethylase (LSD1) by the immunopurification of soluble NFkappaB-p65 chromatin.The sustained upregulation of the NFkappaB-p65 gene as a result of ambient or prior hyperglycemia was associated with increased H3K4m1 but not H3K4m2 or H3K4m3. Furthermore, glucose was shown to have other epigenetic effects, including the suppression of H3K9m2 and H3K9m3 methylation on the p65 promoter. Finally, there was increased recruitment of the recently identified histone demethylase LSD1 to the p65 promoter as a result of prior hyperglycemia.These studies indicate that the active transcriptional state of the NFkappaB-p65 gene is linked with persisting epigenetic marks such as enhanced H3K4 and reduced H3K9 methylation, which appear to occur as a result of effects of the methyl-writing and methyl-erasing histone enzymes.
|LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription.|
Metzger, Eric, et al.
Nature, 437: 436-9 (2005) 2005
Gene regulation in eukaryotes requires the coordinate interaction of chromatin-modulating proteins with specific transcription factors such as the androgen receptor. Gene activation and repression is specifically regulated by histone methylation status at distinct lysine residues. Here we show that lysine-specific demethylase 1 (LSD1; also known as BHC110) co-localizes with the androgen receptor in normal human prostate and prostate tumour. LSD1 interacts with androgen receptor in vitro and in vivo, and stimulates androgen-receptor-dependent transcription. Conversely, knockdown of LSD1 protein levels abrogates androgen-induced transcriptional activation and cell proliferation. Chromatin immunoprecipitation analyses demonstrate that androgen receptor and LSD1 form chromatin-associated complexes in a ligand-dependent manner. LSD1 relieves repressive histone marks by demethylation of histone H3 at lysine 9 (H3-K9), thereby leading to de-repression of androgen receptor target genes. Furthermore, we identify pargyline as an inhibitor of LSD1. Pargyline blocks demethylation of H3-K9 by LSD1 and consequently androgen-receptor-dependent transcription. Thus, modulation of LSD1 activity offers a new strategy to regulate androgen receptor functions. Here, we link demethylation of a repressive histone mark with androgen-receptor-dependent gene activation, thus providing a mechanism by which demethylases control specific gene expression.
|Histone demethylation mediated by the nuclear amine oxidase homolog LSD1.|
Shi, Yujiang, et al.
Cell, 119: 941-53 (2004) 2004
Posttranslational modifications of histone N-terminal tails impact chromatin structure and gene transcription. While the extent of histone acetylation is determined by both acetyltransferases and deacetylases, it has been unclear whether histone methylation is also regulated by enzymes with opposing activities. Here, we provide evidence that LSD1 (KIAA0601), a nuclear homolog of amine oxidases, functions as a histone demethylase and transcriptional corepressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. Lysine demethylation occurs via an oxidation reaction that generates formaldehyde. Importantly, RNAi inhibition of LSD1 causes an increase in H3 lysine 4 methylation and concomitant derepression of target genes, suggesting that LSD1 represses transcription via histone demethylation. The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases.
|A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes.|
Hakimi, Mohamed-Ali, et al.
J. Biol. Chem., 278: 7234-9 (2003) 2003
Eukaryotic genes are under the control of regulatory complexes acting through chromatin structure to control gene expression. Here we report the identification of a family of multiprotein corepressor complexes that function through modifying chromatin structure to keep genes silent. The polypeptide composition of these complexes has in common a core of two subunits, HDAC1,2 and BHC110, an FAD-binding protein. A candidate X-linked mental retardation gene and the transcription initiation factor II-I (TFII-I) are components of a novel member of this family of complexes. Other subunits of these complexes include polypeptides associated with cancer causing chromosomal translocations. These findings not only delineate a novel class of multiprotein complexes involved in transcriptional repression but also reveal an unanticipated role for TFII-I in transcriptional repression.