ChIP Cross-link Gold

Overlapping and distinct functions of SPT6, PNUTS, and PCF11 in regulating transcription termination
Fabienne Bejjani et al.
The histone chaperone and transcription elongation factor SPT6 is integral to RNA polymerase II (RNAPII) activity. SPT6 also plays a crucial role in regulating transcription termination, although the mechanisms involved are largely unknown. In an attempt to identify the pathways employed by SPT6 in this regulation, ...

H2AJ Is a Direct Androgen Receptor Target Gene That Regulates Androgen-Induced Cellular Senescence and Inhibits Mesenchymal Markers in Prostate Cancer Cells
Mehdi Heidari Horestani et al.
Background: Prostate cancer (PCa) is a significant public health issue, particularly in developed countries. The androgen receptor (AR) plays a key role in regulating both the normal development and the proliferation of PCa. Bipolar androgen therapy, which involves treatment with supraphysiological androgen lev...

TEAD-targeting small molecules induce a cofactor switch to regulate the Hippo pathway
Alissa D. Guarnaccia et al.
TEAD proteins are the main transcriptional effectors of the Hippo signaling pathway and a pharmacological target in oncology. Most TEAD-targeting small molecules act by disrupting interaction with the oncogenic transcriptional activators YAP and TAZ. Here, we describe an alternative mechanism for TEAD lipid pocket b...

Therapeutic targeting of EP300/CBP by bromodomain inhibition in hematologic malignancies
Luciano Nicosia et al.
CCS1477 (inobrodib) is a potent, selective EP300/CBP bromodomain inhibitor which induces cell-cycle arrest and differentiation in hematologic malignancy model systems. In myeloid leukemia cells, it promotes rapid eviction of EP300/CBP from an enhancer subset marked by strong MYB occupancy and high H3K27 acetylation,...

Differentiation block in acute myeloid leukemia regulated by intronicsequences of FTO
Camera F. et al.
Iroquois transcription factor gene IRX3 is highly expressed in 20–30\% of acute myeloid leukemia (AML) and contributes to the pathognomonic differentiation block. Intron 8 FTO sequences ∼220kB downstream of IRX3 exhibit histone acetylation, DNA methylation, and contacts with th...

Targeting lymphoid-derived IL-17 signaling to delay skin aging.
Paloma S. et al.
Skin aging is characterized by structural and functional changes that contribute to age-associated frailty. This probably depends on synergy between alterations in the local niche and stem cell-intrinsic changes, underscored by proinflammatory microenvironments that drive pleotropic changes. The nature of these age-...

Mutant FUS induces chromatin reorganization in the hippocampus andalters memory processes.
Tzeplaeff L. et al.
Cytoplasmic mislocalization of the nuclear Fused in Sarcoma (FUS) protein is associated to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cytoplasmic FUS accumulation is recapitulated in the frontal cortex and spinal cord of heterozygous Fus mice. Yet, the mechanisms linking FUS mislocalizati...

Smc5/6 silences episomal transcription by a three-step function.
Abdul F. et al.
In addition to its role in chromosome maintenance, the six-membered Smc5/6 complex functions as a restriction factor that binds to and transcriptionally silences viral and other episomal DNA. However, the underlying mechanism is unknown. Here, we show that transcriptional silencing by the human Smc5/6 complex is a t...

Androgen-Induced MIG6 Regulates Phosphorylation ofRetinoblastoma Protein and AKT to Counteract Non-Genomic ARSignaling in Prostate Cancer Cells.
Schomann T. et al.
The bipolar androgen therapy (BAT) includes the treatment of prostate cancer (PCa) patients with supraphysiological androgen level (SAL). Interestingly, SAL induces cell senescence in PCa cell lines as well as ex vivo in tumor samples of patients. The SAL-mediated cell senescence was shown to be androgen receptor (A...

Soluble guanylate cyclase signalling mediates etoposide resistance inprogressing small cell lung cancer
Schenk MW et al.
Small cell lung cancer (SCLC) has a 5-year survival rate of \<7\%. Rapid emergence of acquired resistance to standard platinum-etoposide chemotherapy is common and improved therapies are required for this recalcitrant tumour. We exploit six paired pre-treatment and post-chemotherapy circulating tumour cell patien...

Regulatory interplay between Vav1, Syk and β-catenin occurs in lungcancer cells.
Boudria Rofia et al.
Vav1 exhibits two signal transducing properties as an adaptor protein and a regulator of cytoskeleton organization through its Guanine nucleotide Exchange Factor module. Although the expression of Vav1 is restricted to the hematopoietic lineage, its ectopic expression has been unraveled in a number of solid tumors. ...

Androgen receptor positively regulates gonadotropin-releasing hormonereceptor in pituitary gonadotropes.
Ryan, Genevieve E. et al.
Within pituitary gonadotropes, the gonadotropin-releasing hormone receptor (GnRHR) receives hypothalamic input from GnRH neurons that is critical for reproduction. Previous studies have suggested that androgens may regulate GnRHR, although the mechanisms remain unknown. In this study, we demonstrated that androgens ...

BAF complexes drive proliferation and block myogenic differentiation in fusion-positive rhabdomyosarcoma
Laubscher et. al.
Rhabdomyosarcoma (RMS) is a pediatric malignancy of skeletal muscle lineage. The aggressive alveolar subtype is characterized by t(2;13) or t(1;13) translocations encoding for PAX3- or PAX7-FOXO1 chimeric transcription factors, respectively, and are referred to as fusion positive RMS (FP-RMS). The fusion gene alters...

The Human Integrator Complex Facilitates Transcriptional Elongation by Endonucleolytic Cleavage of Nascent Transcripts.
Beckedorff F, Blumenthal E, daSilva LF, Aoi Y, Cingaram PR, Yue J, Zhang A, Dokaneheifard S, Valencia MG, Gaidosh G, Shilatifard A, Shiekhattar R
Transcription by RNA polymerase II (RNAPII) is pervasive in the human genome. However, the mechanisms controlling transcription at promoters and enhancers remain enigmatic. Here, we demonstrate that Integrator subunit 11 (INTS11), the catalytic subunit of the Integrator complex, regulates transcription at these loci...

Inactivation of Arid1a in the endometrium is associated with endometrioid tumorigenesis through transcriptional reprogramming.
Suryo Rahmanto Y, Shen W, Shi X, Chen X, Yu Y, Yu ZC, Miyamoto T, Lee MH, Singh V, Asaka R, Shimberg G, Vitolo MI, Martin SS, Wirtz D, Drapkin R, Xuan J, Wang TL, Shih IM
Somatic inactivating mutations of ARID1A, a SWI/SNF chromatin remodeling gene, are prevalent in human endometrium-related malignancies. To elucidate the mechanisms underlying how ARID1A deleterious mutation contributes to tumorigenesis, we establish genetically engineered murine models with Arid1a and/or Pten c...

AP-1 controls the p11-dependent antidepressant response.
Chottekalapanda RU, Kalik S, Gresack J, Ayala A, Gao M, Wang W, Meller S, Aly A, Schaefer A, Greengard P
Selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed drugs for mood disorders. While the mechanism of SSRI action is still unknown, SSRIs are thought to exert therapeutic effects by elevating extracellular serotonin levels in the brain, and remodel the structural and functional alterations ...

A stress-responsive enhancer induces dynamic drug resistance in acute myeloid leukemia.
Williams MS, Amaral FM, Simeoni F, Somervaille TC
The drug efflux pump ABCB1 is a key driver of chemoresistance, and high expression predicts for treatment failure in acute myeloid leukemia (AML). In this study, we identified and functionally validated the network of enhancers that controls expression of ABCB1. We show that exposure of leukemia cells to daunorubici...

The nuclear hypoxia-regulated NLUCAT1 long non-coding RNA contributes to an aggressive phenotype in lung adenocarcinoma through regulation of oxidative stress.
Moreno Leon L, Gautier M, Allan R, Ilié M, Nottet N, Pons N, Paquet A, Lebrigand K, Truchi M, Fassy J, Magnone V, Kinnebrew G, Radovich M, Cheok MH, Barbry P, Vassaux G, Marquette CH, Ponzio G, Ivan M, Pottier N, Hofman P, Mari B, Rezzonico R
Lung cancer is the leading cause of cancer death worldwide, with poor prognosis and a high rate of recurrence despite early surgical removal. Hypoxic regions within tumors represent sources of aggressiveness and resistance to therapy. Although long non-coding RNAs (lncRNAs) are increasingly recognized as major gene ...

P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress.
Bugai A, Quaresma AJC, Friedel CC, Lenasi T, Düster R, Sibley CR, Fujinaga K, Kukanja P, Hennig T, Blasius M, Geyer M, Ule J, Dölken L, Barborič M
DNA damage response (DDR) involves dramatic transcriptional alterations, the mechanisms of which remain ill defined. Here, we show that following genotoxic stress, the RNA-binding motif protein 7 (RBM7) stimulates RNA polymerase II (Pol II) transcription and promotes cell viability by activating the positive transcr...

The BRG1/SOX9 axis is critical for acinar cell-derived pancreatic tumorigenesis.
Tsuda M, Fukuda A, Roy N, Hiramatsu Y, Leonhardt L, Kakiuchi N, Hoyer K, Ogawa S, Goto N, Ikuta K, Kimura Y, Matsumoto Y, Takada Y, Yoshioka T, Maruno T, Yamaga Y, Kim GE, Akiyama H, Ogawa S, Wright CV, Saur D, Takaori K, Uemoto S, Hebrok M, Chiba T, Seno
Chromatin remodeler Brahma related gene 1 (BRG1) is silenced in approximately 10% of human pancreatic ductal adenocarcinomas (PDAs). We previously showed that BRG1 inhibits the formation of intraductal pancreatic mucinous neoplasm (IPMN) and that IPMN-derived PDA originated from ductal cells. However, the role of BR...

A new metabolic gene signature in prostate cancer regulated by JMJD3 and EZH2.
Daures M, Idrissou M, Judes G, Rifaï K, Penault-Llorca F, Bignon YJ, Guy L, Bernard-Gallon D
Histone methylation is essential for gene expression control. Trimethylated lysine 27 of histone 3 (H3K27me3) is controlled by the balance between the activities of JMJD3 demethylase and EZH2 methyltransferase. This epigenetic mark has been shown to be deregulated in prostate cancer, and evidence shows H3K27me3 enri...

SMC Progressively Aligns Chromosomal Arms in Caulobacter crescentus but Is Antagonized by Convergent Transcription
Tran N.T. et al.
The structural maintenance of chromosomes (SMC) complex plays an important role in chromosome organization and segregation in most living organisms. In Caulobacter crescentus, SMC is required to align the left and the right arms of the chromosome that run in parallel down the long axis of the cell. However, the...

EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells
Beringer M. et al.
The cellular plasticity of pluripotent stem cells is thought to be sustained by genomic regions that display both active and repressive chromatin properties. These regions exhibit low levels of gene expression, yet the mechanisms controlling these levels remain unknown. Here, we describe Elongin BC as a binding fact...