DiaMag protein G-coated magnetic beads (ChIP-seq grade)

Identification of an E3 ligase that targets the catalytic subunit ofRNA polymerase I upon transcription stress.
Pitts Stephanie et al.
RNA polymerase I (Pol I) synthesizes ribosomal RNA (rRNA), which is the first and rate-limiting step in ribosome biogenesis. Factors governing the stability of the polymerase complex are not known. Previous studies characterizing the Pol I inhibitor BMH-21 revealed a transcriptional stress-dependent pathway for degr...

Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage.
Ait-Ammar A. et al.
HIV-1 latency generates reservoirs that prevent viral eradication by the current therapies. To find strategies toward an HIV cure, detailed understandings of the molecular mechanisms underlying establishment and persistence of the reservoirs are needed. The cellular transcription factor KAP1 is known as a potent rep...

ZNF354C is a transcriptional repressor that inhibits endothelialangiogenic sprouting.
Oo, James A and Irmer, Barnabas and Günther, Stefan and Warwick, Timothyand Pálfi, Katalin and Izquierdo Ponce, Judit and Teichmann, Tom andPflüger-Müller, Beatrice and Gilsbach, Ralf and Brandes, Ralf P andLeisegang, Matthias S
Zinc finger proteins (ZNF) are a large group of transcription factors with diverse functions. We recently discovered that endothelial cells harbour a specific mechanism to limit the action of ZNF354C, whose function in endothelial cells is unknown. Given that ZNF354C has so far only been studied in bone and tum...

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 ...

Aging-regulated anti-apoptotic long non-coding RNA Sarrah augments recovery from acute myocardial infarction.
Trembinski DJ, Bink DI, Theodorou K, Sommer J, Fischer A, van Bergen A, Kuo CC, Costa IG, Schürmann C, Leisegang MS, Brandes RP, Alekseeva T, Brill B, Wietelmann A, Johnson CN, Spring-Connell A, Kaulich M, Werfel S, Engelhardt S, Hirt MN, Yorgan K, Eschen
Long non-coding RNAs (lncRNAs) contribute to cardiac (patho)physiology. Aging is the major risk factor for cardiovascular disease with cardiomyocyte apoptosis as one underlying cause. Here, we report the identification of the aging-regulated lncRNA Sarrah (ENSMUST00000140003) that is anti-apoptotic in cardiomyocytes...

Inhibition of histone deacetylation rescues phenotype in a mouse model of Birk-Barel intellectual disability syndrome.
Cooper A, Butto T, Hammer N, Jagannath S, Fend-Guella DL, Akhtar J, Radyushkin K, Lesage F, Winter J, Strand S, Roeper J, Zechner U, Schweiger S
Mutations in the actively expressed, maternal allele of the imprinted KCNK9 gene cause Birk-Barel intellectual disability syndrome (BBIDS). Using a BBIDS mouse model, we identify here a partial rescue of the BBIDS-like behavioral and neuronal phenotypes mediated via residual expression from the paternal Kcnk9 (Kcnk9...

H3K4me1 Supports Memory-like NK Cells Induced by Systemic Inflammation.
Rasid O, Chevalier C, Camarasa TM, Fitting C, Cavaillon JM, Hamon MA
Natural killer (NK) cells are unique players in innate immunity and, as such, an attractive target for immunotherapy. NK cells display immune memory properties in certain models, but the long-term status of NK cells following systemic inflammation is unknown. Here we show that following LPS-induced endotoxemia in mi...

Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.
Aloia L, McKie MA, Vernaz G, Cordero-Espinoza L, Aleksieva N, van den Ameele J, Antonica F, Font-Cunill B, Raven A, Aiese Cigliano R, Belenguer G, Mort RL, Brand AH, Zernicka-Goetz M, Forbes SJ, Miska EA, Huch M
Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal ...

Interaction of Sox2 with RNA binding proteins in mouse embryonic stem cells.
Samudyata , Amaral PP, Engström PG, Robson SC, Nielsen ML, Kouzarides T, Castelo-Branco G
Sox2 is a master transcriptional regulator of embryonic development. In this study, we determined the protein interactome of Sox2 in the chromatin and nucleoplasm of mouse embryonic stem (mES) cells. Apart from canonical interactions with pluripotency-regulating transcription factors, we identified interactions with...

The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity
Domínguez-Andrés Jorge, Novakovic Boris, Li Yang, Scicluna Brendon P., Gresnigt Mark S., Arts Rob J.W., Oosting Marije, Moorlag Simone J.C.F.M., Groh Laszlo A., Zwaag Jelle, Koch Rebecca M., ter Horst Rob, Joosten Leo A.B., Wijmenga Cisca, Michelucci Ales
Sepsis involves simultaneous hyperactivation of the immune system and immune paralysis, leading to both organ dysfunction and increased susceptibility to secondary infections. Acute activation of myeloid cells induced itaconate synthesis, which subsequently mediated innate immune tolerance in human monocytes. In con...

The histone demethylase Jarid1b mediates angiotensin II-induced endothelial dysfunction by controlling the 3'UTR of soluble epoxide hydrolase.
Vasconez AE, Janetzko P, Oo JA, Pflüger-Müller B, Ratiu C, Gu L, Helin K, Geisslinger G, Fleming I, Schröder K, Fork C, Brandes RP, Leisegang MS
AIM: The histone demethylase Jarid1b limits gene expression by removing the active methyl mark from histone3 lysine4 at gene promoter regions. A vascular function of Jarid1b is unknown, but a vasoprotective function to inflammatory and hypertrophic stimuli, like angiotensin II (AngII) could be inferred. This hypothe...

Epigenetic regulation of brain region-specific microglia clearance activity.
Ayata P, Badimon A, Strasburger HJ, Duff MK, Montgomery SE, Loh YE, Ebert A, Pimenova AA, Ramirez BR, Chan AT, Sullivan JM, Purushothaman I, Scarpa JR, Goate AM, Busslinger M, Shen L, Losic B, Schaefer A
The rapid elimination of dying neurons and nonfunctional synapses in the brain is carried out by microglia, the resident myeloid cells of the brain. Here we show that microglia clearance activity in the adult brain is regionally regulated and depends on the rate of neuronal attrition. Cerebellar, but not striatal or...

Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx.
Hensel KO, Cantner F, Bangert F, Wirth S, Postberg J
BACKGROUND: In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of cccDNA and HBx remains unexplored. RESULTS: To identify virus-host genome...

Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function.
Josipovic I, Pflüger B, Fork C, Vasconez AE, Oo JA, Hitzel J, Seredinski S, Gamen E, Heringdorf DMZ, Chen W, Looso M, Pullamsetti SS, Brandes RP, Leisegang MS
Sphingosine-1-Phosphate (S1P) is a potent signaling lipid. The effects of S1P are mediated by the five S1P receptors (S1PR). In the endothelium S1PR1 is the predominant receptor and thus S1PR1 abundance limits S1P signaling. Recently, lncRNAs were identified as a novel class of molecules regulating gene expression. ...

Metabolic Induction of Trained Immunity through the Mevalonate Pathway.
Bekkering S, Arts RJW, Novakovic B, Kourtzelis I, van der Heijden CDCC, Li Y, Popa CD, Ter Horst R, van Tuijl J, Netea-Maier RT, van de Veerdonk FL, Chavakis T, Joosten LAB, van der Meer JWM, Stunnenberg H, Riksen NP, Netea MG
Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that activation of the cholesterol synthesis pathway, but not the synthesis of...

BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity.
Arts RJW, Moorlag SJCFM, Novakovic B, Li Y, Wang SY, Oosting M, Kumar V, Xavier RJ, Wijmenga C, Joosten LAB, Reusken CBEM, Benn CS, Aaby P, Koopmans MP, Stunnenberg HG, van Crevel R, Netea MG
The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide epigenetic repr...

Polycomb repressive complex 2 (PRC2) silences genes responsible for neurodegeneration
von Schimmelmann M et al.
Normal brain function depends on the interaction between highly specialized neurons that operate within anatomically and functionally distinct brain regions. Neuronal specification is driven by transcriptional programs that are established during early neuronal development and remain in place in the adult brain. The...