Gene #promoters are intrinsically hardwired for release of paused #RNApolymerase by H2A.Z; This Primer explores a new @PLOSBiology study showing that poly(dA) tracts at promoters positively stimulate H2A.Z incorporation by the SWR complex in yeast. Paper: https://plos.io/4kggWyD Primer: https://plos.io/4dihoKK
H2A.Z deposition by the SWR complex is stimulated by polyadenine DNA sequences in nucleosomes

The variant histone H2A.Z is deposited into nucleosomes immediately downstream of promoters, where it plays a critical role in transcription. The site-specific deposition of H2A.Z is catalyzed by the SWR complex, a conserved chromatin remodeler with affinity for promoter-proximal nucleosome-depleted regions (NDRs) and histone acetylation. By comparing the genomic distribution of H2A.Z in wild-type and SWR-deficient cells, we found that SWR is also responsible for depositing H2A.Z at thousands of non-canonical sites not directly linked to NDRs or histone acetylation. To understand the targeting mechanism of H2A.Z, we presented SWR to a library of canonical nucleosomes isolated from yeast and analyzed the preferred substrates. Our results revealed that SWR preferentially deposited H2A.Z into a subset of endogenous H2A.Z sites, which are overrepresented by polyadenine tracts on the top strands of the DNA duplex at the nucleosomal entry-exit sites. Insertion of polyadenine sequences into recombinant nucleosomes near the outgoing H2A-H2B dimer enhanced SWR’s affinity for the nucleosomal substrate and increased its H2A.Z insertion activity. These findings suggest that the genome encodes sequence-based information that facilitates remodeler-mediated targeting of H2A.Z.

The latent cis-regulatory potential of mobile DNA

Transposable elements can alter gene regulation in their host genome, either when they integrate into a genome, or when they accrue mutations after integration. However, the extent to which transposons can alter gene expression, as well as the necessary mutational steps, are not well characterized. Here we study the gene regulatory potential of the prominent IS3 family of transposable elements in E.coli . We started with 10 sequences from the ends of 5 IS3 sequences, created 18,537 random mutations in them, and measured their promoter activity using a massively parallel reporter assay. All 10 sequences could evolve de-novo promoter activity from single point mutations. De-novo promoters mostly emerge from existing proto-promoter sequences when mutations create new −10 boxes downstream of preexisting −35 boxes. The ends of IS3s harbor ~1.5 times as many such proto-promoter sequences than the E. coli genome. We also estimate that at least 26% of the 706 characterized IS3s already encode promoters. Our study shows that transposable elements can have a high latent cis-regulatory potential. Our observations can help to explain why mobile DNA may persist in prokaryotic genomes. They also underline the potential use of transposable elements as a substrate for evolving new gene expression. ### Competing Interest Statement The authors have declared no competing interest.

bioRxiv

With female promoters - night club "Crystal" - Smederevo, Serbia - april 2018

#female #promoters #nightclub #crystal #smederevo #serbia #photos #photography #sexygirls #sexlover #milošsomborac

Weight-loss drugs ‘slow down the ageing process’, scientists find

🔥Ozempic has ‘far-reaching benefits’ beyond weight loss with people dying at lower rate from all causes

❇️ Weight-loss drugs are poised to revolutionise healthcare by
slowing down the ageing process and by allowing people to live for longer and in better health.

That is the dramatic message from leading scientists after studies were presented last week at the European Society of Cardiology Conference in London.

Research has already found that #semaglutide
– also known by the brand names #Wegovy and #Ozempic
– reduced the risk of death in people who were obese or overweight and had cardiovascular disease.

But fresh studies have found that Ozempic has impacts beyond what was originally imagined for the drug.

✅People who took the drug died at a lower rate from all causes, not just from cardiovascular causes, researchers discovered.

“Semaglutide has far-reaching benefits beyond what we initially imagined,” said Prof Harlan Krumholz of the Yale school of medicine.

“It’s not just avoiding heart attacks. These are #health #promoters.

It wouldn’t surprise me that improving people’s health this way actually slows down the ageing process.”

The studies were produced from the Select trial in the US,
which studied 17,604 people aged 45 or older who were overweight or obese
and had established cardiovascular disease but not diabetes.

They received semaglutide or a placebo and were tracked for more than three years.

https://www.theguardian.com/science/article/2024/aug/31/weight-loss-drugs-ozempic-slow-down-ageing-process-study?CMP=Share_iOSApp_Other

Weight-loss drugs ‘slow down the ageing process’, scientists suggest

Semaglutide – contained in Ozempic and Wegovy – has ‘far-reaching benefits’, with people dying at lower rate from all causes

The Guardian
Where do new genes come from? @HassanZaman91 @barricklab &co show that within the timescale of the #LTEE experiment, the co-option of #promoters, mainly from #TransposableElements, serves as the major source of raw material for #DeNovoGenes #PLOSBiology https://plos.io/4a8p6DT
Promoter recruitment drives the emergence of proto-genes in a long-term evolution experiment with Escherichia coli

De novo gene birth from non-genic sequence has received considerable attention due to the widespread occurrence of genes that are unique to particular species. This study shows that within the short evolutionary timescale of the iconic E. coli LTEE experiment, the co-option of promoters, principally from transposable elements, serves as the major source of raw material for new genes.

The bear & leather communities have a big racism problem - LGBTQ Nation

People of color cannot freely exist in queer spaces. Its time to hold business owners and event promoters accountable.

LGBTQ Nation
How Can We Make Atlanta Black Gay Pride More Age Inclusive?

News, events, features, entertainment, interviews, Pride, nightlife, organizations, families, marriage

Georgia Voice - Gay & LGBT Atlanta News
Belgian Waffle Ride founder addresses new trans athlete policy

Michael Marckx says new rules will protect "integrity and parity." Promoters of other gravel races say they have no plans to change rules of inclusion. 

Velo

To fellow #musicians #promoters #indieartists

ahhhhh I got like 40 plus declines from #spotify #playlists via #submithub.
the tone of the #music doesn't fit: too #dramatic, too #dark.
This might have been the hardest song I could have started with.
Most people want an uneventful background playing playlist with no surprises. I already contacted only the "sad mood" ones.

Can anyone give me advise wich genre might fit best? More divers playlists might be open?🙏
The song: https://youtu.be/yU32xlu10XM

Those Who Throw a Stone - Grandios Sensibel (Musikvideo)

YouTube