Yin Yang 1 requires Endotoxin to activate Germline DNA transcription and Class Switch Recombination

Autism, Schizophrenia, Cancer, other diseases from foreign DNA in Jabs can be explained by looking at the Synergy of Zinc Finger Protein YY1 and co-contaminant Endotoxin. The SV40 enhancer connection!

Gathering some more thoughts on how foreign DNA in Jabs could end up changing the Human Genome as well as causing immense suffering.

Thanks to my friend and lawyer Julian Gillespie who sent me this screenshot from John Campbell discussing the letters, one of which I co-signed, in support of Russell Broadbent MP demanding that Australian Prime Minister Anthony Albanese sit up and take notice.¹²

John Campbell on Russell Broadbent Letter

The link arrived just as I was preparing this article prompted by my friend Maria Gutschi who had close encounters with Nobel Prize winners at a recent mRNA jab conference³, I found myself plummeting down a new, but rewarding rabbit hole.

The key was the early work of one speaker, 80-year-old Phillip Allen Sharp⁴, who shared the 1993 Nobel Prize with Richard John Roberts⁵ for the “Split Gene” or Gene Splicing.

They discovered that genes in eukaryotes are not contiguous strings but contain introns, and that the splicing of messenger RNA to delete those introns can occur in different ways, yielding different proteins from the same DNA sequence.

Their work was later expanded by many clever scientists.

That took me to learn a little about Oncogenic Late SV40 factor (LSF, also known as CP-2, TFCP2, or LBP-1)⁶ and Yin Yang 1 protein.

Transcription Factor Yin Yang 1

Here is the 1996 crystal structure of Yin Yang 1 protein binding to a segment of DNA.⁷

Notice the Zinc atoms. Early in 2023 I mentioned the importance of our numerous Zinc enzymes.⁸

Here is the Figure caption:

FIG. 2. Structure of the Δ YY1–initiator element complex. (A) Stereoview of the Δ YY1–DNA complex. The protein is shown as a ribbon representation, the DNA as a stick model, and the zinc ions as spheres. YY1 zinc fingers are colored red, yellow, green, and blue from N to C termini.

The template strand of the DNA is colored grey, with the nucleotides corresponding to the two transcription start sites shown in purple, and the nontemplate strand is colored black. RNA synthesis proceeds downwards in this view. (B) Schematic representation of the Δ YY1–DNA interactions.

The complete sequence of the crystallization oligonucleotide is shown, with the template strand labeled ‘‘T.’’ Protein–DNA contacts are color coded as in A by their zinc finger of origin. Supporting interactions that stabilize side chains making DNA contacts are also shown in italic. The two transcription start sites are labeled with arrows denoting the direction of transcription. Enthalpically favorable interactions include salt bridges (<4 Å), hydrogen bonds (<3.5 Å), van der Waals contacts (<4 Å), and a number of water-mediated bridges (denoted with ‘‘w’’).

(C) Space-filling representation of the Δ YY1–DNA complex. The protein and DNA are colored as in A, with the nucleotides corresponding to the two transcription start sites on the template strand shown in white. (D) Space-filling representations of the Δ YY1–P5 promoter complex (Upper) and the complex of TBP and the adenovirus major late promoter (AdMLP) (Lower). Δ YY1 and TBP are colored blue and the template and nontemplate strands of the DNA are colored green and yellow, respectively. The transcription start sites are denoted with white base pairs. A transparent cylinder surrounds the 224 to 231 region of the P5 promoter (the TATA element in the AdMLP).

My head spins reading that!

YY1 and HIV AIDS

In 1994 Margolis and coworkers showed how Human transcription factor YY1 represses Human Immunodeficiency Virus type 1 transcription and virion production.⁹ This helped to explain 1991 observation that the cellular protein LBP-1 specifically repressed transcription in vitro by binding to the upstream site (site II), which overlaps the TATA as an element important in HIV-1 latency.¹⁰

In 1999 Romerio and Margolis presented further details of YY1 and SV40 in their HIV studies annd pointed to then unanswered questions.¹¹

a novel regulatory DNA element, named IST (Initiator of Short Transcripts), has been shown to be present in the HIV-1 LTR (position (-)5 to (+)26), encompassing the binding site for transcription factors YY1 and late SV40 transcription factor (LSF, or CP-2, or LBP-1) (see refs. 2 and 3). IST directs the RNA polymerase II to synthesize short (59-61 nt), correctly initiated, nonpolyadenylated transcripts that prematurely terminate at the TAR stem-loop structure.

SV40 Late Transcription Factor = LBP-1 recognizes Endotoxin and its Lipid A

LPS-binding protein (LBP) is a soluble 60-kDa glycoprotein that recognizes and binds the Lipid A moiety of LPS, enhancing host immune response to Endotoxin.¹²

Late SV40 factor (LSF, also known as CP-2, TFCP2, or LBP-1 is expressed in 27 Human tissues.

Remember that Endotoxin Lipid A is Pfizer’s preferred “adjuvant”.

“LBP is homologous to other phospholipid transport proteins and functions as a transport protein that disaggregates soluble LPS and presents it to targets on cellular membranes”.¹³¹⁴

LPB-1 is also known as Fatty acid-binding protein homolog 1.¹⁵

Endotoxin Class-Switching Activator causes YY1 to be released

In 2003 Barbara Birshtein and coworkers reported that Endotoxin acts to release YY1 by causing hyperphosphorylation of Retinoblastoma Protein (Rb) and produced Class Switching in Splenic B Cells.¹⁶ They showed that YY1 is confined to the cell nucleus.

The cascade of events initiated by LPS that results in activation of GT by 3’ enhancers may open the Igh locus at the chromatin level. LPS has been reported to down-regulate the Bach2 repressor of hs3 and potentially other 3’ Igh enhancers (18). In our studies, we show that LPS induces YY1 binding to both hs3 and the intronic enhancer, both of which are candidates for involvement in CSR (Class Switch Recombination). Addition of E
μ to a combination of all four 3’ Igh enhancers results in strong transcriptional synergy at all stages of B cell differentiation (41, 65). YY1 may also bind to some switch promoters via interaction with the late SV40 factor (LSF) (66), bringing these regions into proximity with the Igh enhancers. Various models have been proposed to explain how a distant enhancer locus, such as the 3’ Igh regulatory region, is able to mediate long distance regulation. Perhaps YY1 serves as a nucleating protein for an Igh holocomplex (67), in which LPS stimulation results in a looping out of the intervening sequence and places the 3’ regulatory region in close proximity with the switch promoters, intronic enhancer, and/or VH promoters. YY1 interacts with components of the basal transcription machinery, such as TFIIB, TBP, and TAFII55 (58, 68), that may also be associated with such a complex.

Also of interest to Class Switching specialists will be the 2009 paper by Karen Repetny and coworker looking at Splenic B cells in vivo.¹⁷ They found that LBP-1a is the dominant family member expressed in mouse primary B lymphocytes.

First, we demonstrate that leader-binding protein-1a (LBP-1a) is the prevalent family member in B lymphocytes. Second, we demonstrate by ChIP that LBP-1a binds genomic sequences around mouse switch (S) regions in an isotype-specific manner, in accordance with computational predictions: binding is observed to Sμ and Sα, but not to the tested Sγ1, regions. Importantly, binding of LBP-1a is tightly regulated, with occupancy at genomic S regions dramatically decreasing following LPS (Endotoxin) stimulation.

A 2014 paper by Janet Stavnezer and Carol E. Schrader discussed developments in understanding of IgH Chain Class Switch Recombination and the importance of Endotoxin is highlighted.¹⁸

The Wikipedia page on Class-Switch Recombination, also known as Immunoglobulin Class Switching, Isotype Switching or Isotypic Commutation has no references beyond 2020.¹⁹

Autism and Schizophrenia and YY1 SNPs

Father of my distant cousin, anti-Fluoridation and anti-Mercury Filling Dentist Maria Claudianos, is Charles Claudianos, a world-leading researcher on Brain development.

He and coworkers reported 12 Autism and 13 Schizophrenia Single Nucleotide Polymorphisms (SNPs) associated with seven validated Transcription Factor (TF) binding sites including YY1.²⁰

YY1 causes Mood changes and Cognitive Impairment in Depression

A 2022 paper from China found that the YY1–NF-κB–IL-1β inflammatory pathway is involved in other Brain injury.²¹ They studied YY1 in Humans and Rats where Glucose metabolism in the Hippocampus, Entorhinal Cortex, Amygdala, Striatum, and Medial Prefrontal Cortex were affected. They used a drug to reverse the effects.

Late SV40 Promoter discovered by Kevin McKernan in Pfizer Plasmid

In June 2023, Kevin McKernan shocked the world by independently analyzing the sequence code for Pfizer DNA Plasmid. He showed that the company deliberately withheld crucial information involving the Simiam Virus 40 gene insertion that drives translation in the nucleus of our cells and that of the E coli bacteria usd for cheap production. Here is his announcement Figure.²²

Kevin is also famous for measurement of 19 EU/ml Endotoxin in a Pfizer Jab.

PubMed returned 221 papers dating back to 1972 on SV40. It is also known by a number of synonyms including TFCP2, which pulls up 182 papers.²³²⁴

The SV40 Late Promoter was characterized in 1989 by Dynan and Chervitz who stated that the full 72 base pair sequence was not essential.²⁵

In 1999, Dean and coworkers published this useful model for sequence specific nuclear import of Plasmid DNA.²⁶

(A) Sequence elements and binding sites for transcription factors are shown for the 366 bp SV40 DNA nuclear targeting sequence. (B) Since these transcription factors are synthesized in the cytoplasm, once plasmid DNA has entered the cytoplasm by transfection, injection, or infection, the newly synthesized proteins can bind to the plasmid DNA to form a DNA-protein complex. Thus, the DNA is coated with NLSs (Nuclear Localization Sequences) from the transcription factors, allowing the NLS-mediated import machinery to recognize DNA as a substrate and target it into the nucleus.

YY1 and Late SV40 in Cancer

See reference 18 for links to 121 publications that have cited it, with many involving Cancer.

Of particular relevance to my recent article on Head and Neck Cancer caused by Covid19 Jabs²⁷, Austrian researchers showed in 2021 that YY1 and Late SV40 Factor are markers for poor prognosis.²⁸

Vietnam Vets and their Children get YY1 Lymphoma

The US Defense department takes particular interest in the B-cell Lymphoma, Hodgkin’s, Non-Hodgkin’s and Lymphocytic Leukemia in Veterans and their Children caused by YY1. Here is a grant summary.²⁹

Finding the name of the principal researcher enabled me to hunt for more publications.

In 2003 Atchison used Flys and Maggots³⁰ to study YY1.

In 2011 Atchison published a very useful review of work to that year.³¹

In 2013 Atchison YY1 research was funded by the NIH.³²

The abstract reads:

Conditional knock-out (KO) of Polycomb Group (PcG) protein YY1 results in pro-B cell arrest and reduced immunoglobulin locus contraction needed for distal variable gene rearrangement. The mechanisms that control these crucial functions are unknown. We deleted the 25 amino-acid YY1 REPO domain necessary for YY1 PcG function, and used this mutant (YY1ΔREPO), to transduce bone marrow from YY1 conditional KO mice. While wild-type YY1 rescued B-cell development, YY1ΔREPO failed to rescue the B-cell lineage yielding reduced numbers of B lineage cells. Although the IgH rearrangement pattern was normal, there was a selective impact at the Igκ locus that showed a dramatic skewing of the expressed Igκ repertoire. We found that the REPO domain interacts with proteins from the condensin and cohesin complexes, and that YY1, EZH2 and condensin proteins co-localize at numerous sites across the Ig kappa locus. Knock-down of a condensin subunit protein or YY1 reduced rearrangement of Igκ Vκ genes suggesting a direct role for YY1-condensin complexes in Igκ locus structure and rearrangement.

Another paper in 2014.³³

In 2020 Atchison used knock-out of YY1 in Splenic B cells and found that it affects expression of 1129 genes, with 59 being mitochondrial-related genes.³⁴

The abstract:

Immunoglobulin class switch recombination (CSR) occurs in activated B cells with
increased mitochondrial mass and membrane potential. Transcription factor Yin Yang 1 (YY1) is critical for CSR and for formation of the DNA loops involved in this process. We therefore sought to determine if YY1 knockout impacts mitochondrial gene expression and mitochondrial function in murine splenic B cells, providing a potential mechanism for regulating CSR. We identified numerous genes in splenic B cells differentially regulated when cells are induced to undergo CSR. YY1 conditional knockout caused differential expression of 1129 genes, with 59 being mitochondrial-related genes. ChIP-seq analyses showed YY1 was directly bound to nearly half of these mitochondrial-related genes.
Surprisingly, at the time when YY1 knockout dramatically reduces DNA loop formation and CSR, mitochondrial mass and membrane potential were not significantly impacted, nor was there a significant change in mitochondrial oxygen consumption, extracellular acidification rate, or mitochondrial complex I or IV activities. Our results indicate that YY1 regulates numerous mitochondrial-related genes in splenic B cells, but this does not account for the impact of YY1 on CSR or long-distance DNA loop formation

In 2024 Atchison reported on YY1 involvement in B cell and T cell differentiation.³⁵

The abstract:

During B cell development, cells progress through multiple developmental stages with the pro-B cell stage defining commitment to the B cell lineage. YY1 is a ubiquitous transcription factor that is capable of both activation and repression functions. We find here that knockout of YY1 at the pro-B cell stage eliminates B lineage commitment. YY1 knockout pro-B cells can generate T lineage cells in vitro using the OP9- DL4 feeder system, as well as in vivo after injection into sub-lethally irradiated Rag1^-/- mice. These T lineage-like cells lose their B lineage transcript profile and gain a T cell lineage profile. Single cell-RNA-seq experiments showed that as YY1 knockout pro-B cells transition into T lineage cells, various cell clusters adopt transcript profiles representing a multiplicity of hematopoietic lineages indicating unusual lineage plasticity. Given the ubiquitous nature of YY1 and its dual activation and repression functions, YY1 likely regulates commitment in multiple cell lineages.

Endotoxin Jabbing of Humans increases YY1

Male volunteers from the Netherlands jabbed with as little as 1 nanogram per kilogram saw increase of YY1 and other transcription factors within 4 hours.³⁶

Summary

Endotoxin releases YY1 that together with SV40 causes catastrophy, opening the pathways to foreign DNA fragment damage. Please share with any genomics experts you think might be interested so we can get some discussion going.

Some related topics

Zinc compounds have been used to make Endotoxin detectors.³⁷

Tromethamine inhibits Zinc enzymes.³⁸

Inducible Nitric-oxide Synthase is a Zinc enzyme.³⁹

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3. The Ribo-Club Conference and RNA Canada

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