HYPB in Embryonic Vascular Development

HYPB IN EMBRYONIC VASCULAR DEVELOPMENT 7

HYPBin Embryonic Vascular Development

HYPBin Embryonic Vascular Development

Thehistone known as Histone H3 lysine 36 methyltransferase abbreviatedas HYPB is a histone of humans of type H3 lysine 36(H3K36).Thishistone is also a specific methyltransferase which also acts as the amajor ortholog to yeast of set2.this research mainly aimed atexploring and investigating the major physiological function of thehuman Histone H3 lysine 36 methyltransferase. In this research, themice where used extensively as the specimen in the course of thestudy. This study also aimed at finding out other Histones apart fromHYPB for instance the mammalian H3K36 HMTs (5) in relation to howthey play a role in regulating the H3K36 methylation and theexpression of the target genes during the process of development.

Thisresearch also had a goal of investigating how the HYPB can take partduring the process of development of an embryo in womb a processreferred to as embryogenesis in science. It further wanted toinvestigate how the other histones like H3K36HMTs can work hand inhand with the H3K36me1/2 histone in the entire embryogenesis process.The genes that are significantly altered by the disruption of theHYPB were also significantly studied in this research.it alsoentailed studying the vital and potential roles of the HYPB togethera different histone called H3K36 methylation on the various genesthat are involved in the embryogenesis process.

Thusthe research entailed finding out the general role played by the HYPBin the overall process of embryonic and vascular remodeling. Thiswould in the end be used as a vital tool in studying the majorfunction played by the H3K36 methylation in the biological process ofvasculogenesis or angiogenesis during the entire embryogenesis cycle.

Thisresearch was driven by number of hypotheses which included thefollowing:

  • The disruption of the H3K36me3 and also results into embryonic lethality

  • There are exists a number of vascular defects in the HYPB embryos

  • There exist a number of vascular defects in the HYPB an embryo.

  • There exist a number of vascular defects in the HYPB yolks sacs.

  • The Labyrinth layer architecture of the HYPB placenta is defective

  • The WT tetraploid and extra embryonic tissues cannot necessarily rescue the HYPB phenotypes.

  • The disruption of HYPB also alters the gene expression that is involved in the vascular remodeling.

  • The HYPB is hugely required in the formation of vessels mainly in the ES cell which is derived from the EBs.

  • The knockdown of the HYPB in the endothelial cells of humans also impairs the migration and the tubule activities involved in the formation.

Previousresearch of the subject has revealed that the development of themulticellular organisms is very fundamental and crucial to thedevelopment of the successive processes. The process in which thesingle cells normally give rise to the very many types of cells,these cells in the end exert a number of functions and they alsoorganize themselves in the formation of the general adult plan of thebody.

Thusto effectively gain control of the entire development, one of themost vital and fundamental roles that any organism needs to playentails the spatial and the also the temporal regulation ofexpression of the numerous genes. Previous research has also shownthat the mechanisms in the process of transcription control theentire gene expression. They do this by recognizing the elements ofDNA and the recruitment of the transcription machinery which is verygeneral. This machinery should also be q covalent modification of themammalian histones that are in many cases mediated by the families ofthe enzymatic cofactors. These cofactors have emerged has the majorregulatory mechanisms that are involved in the process of geneexpression.

Thesenumerous gene modifications also play a very vital role in theregulation of gene expression thus significantly altering theaccessibility for the transcription of the machineries. These genescould as well serve as the epigeneticsystem of marking theepigenetic marking system is also vital in maintaining the horrifyingprograms of the gene expression mainly during the process involvingthe cellular differential and development of the organism. HYPB isalso being referred to as the hSETD2, HSPC069, KMT3A and SETD2.TheHYPB mammalian histone has been referred as to as themethyltransferase (HMT).

Theprevious research also indicates that this HSPC069 was initiallysequestered from the hematopoietic stem cells. The encoded proteinmatter was also obtained as a major factor that also interact withthe protein disease known as the huntingtin (9).An a number ofprevious research on the subject indicated HYPB as a major histoneH3K36 specific histone methyltransferase(HMT) which also interactswith the hyperphosphorylatedRNA polymerase II (pol II) (10).

Thebasic design of the experiment of the research involved the use ofknockout mice will be used in the exploration of the function of themammalian histone called HYPB in the development context. Thevascular defects in the HYPBembryos, the placentas and the yolk sacswill be detailed. This will be done through very extensive andall-encompassinghistological analyses and proper gene expression andprofiling. The tetraploid assay of complementation was also utilizedin this study. This was mainly to examine the probability of thephenotypes being brought about by the extra embryonic tissues. In thevitro cultured stem cell of embryo was used in the investigation ofthe major role played by the HYPB in the vascular development at thelevel of a cell.

Theresults of the analysis indicated that resistant cells that werescreened using the PCR as demonstrated and were also verified.Theresultsindicated that the TK-neo cassette that was inserteddisrupted the HYPB and the ORF genethis also led to the abolishmentof the SET domains together with the downstream domains. The embryosarising out of the heterozygous crosses were collected. The genotypesof these were also monitored using the genomic PCR. The mammalianhistone methylation embryo states were determined using the westernblot. The results obtained showed that the H3K36me3and not H3K36me1/2 were impaired by the disruption of HYPB.

Theresults indicated that the gene expression profile shows that manyimportant and vital hematopoietic genes were not attracted by thepurported HYPB disruption. The results demonstrated a very normalseparation and growth of the erythrocytes in the mutant mice. Thisgives a suggestion that the disturbance of HYPB could disturb thegrowth of the blood vessels rather than the red blood cells at theembryonic stage of development.th results provided further evidencesupporting the assumption that the endothelial differentiation of thecells were detected in the HYPB yolk sac by the IHC and theconsequent section analysis.

Inconclusion, epigenetics play a key role in embryonic andcardiovascular development. Epigenetic mechanisms such as histone andDNA highly control the progenitor cells and epigenentic celldevelopment. Variations in methylation and histone acetylation restricted by histone deacetylases / acetylases regulates access oftranscription factors hence modulating the chromatin structure. Thehistone family controls stem cell differentiation, maintenance andfunction. Chromatin remodellig is affected by enzymes that modifyhistones. Histone- H3K36 controls the embryonic stem celldifferentiation into a primitive endoderm. Therefore, it plays a keyrole in regulating gene expression, hence controlling the developmentprocess. H3K36 plays a role in molecular functions such assuppression of cryptic transcription, transcriptional elongation andm RNA export. From the study, we identified that HYPB play a role ingene alteration it is not evident if H3K36 plays a role in specifiedgrowth progression.

Furtherresearch question: what could be a possible replacement for HYPB inthe process of embryogenesis?

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