General Control Mechanism Research Articles

Microbial Synthetic Epigenetic Tools Design and Applications.

Microbial synthetic epigenetics offers significant opportunities for the design of synthetic biology tools by leveraging reversible gene control mechanisms without altering DNA sequences. However, limited understanding and a lack of technologies for thorough analysis of the mechanisms behind epigenetic modifications have hampered their utilization in biotechnological applications. In this review, we explore advancements in developing epigenetic-based synthetic gene regulatory tools at both transcriptional and post-transcriptional levels. Furthermore, we examine strategies developed to construct epigenetic-based circuits that provide controllable and stable gene regulation, aiming to boost the performance of microbial chassis cells. Finally, we discuss the current challenges and perspectives in the development of synthetic epigenetic tools.

Parameter adaptive based neural network sliding mode control for electro‐hydraulic system with application to rock drilling jumbo

SummaryRock drilling jumbo is an important large construction machine used for tunneling construction, and its automation has an urgent demand in engineering. However, the electro‐hydraulic system of the rock drilling jumbo has strong parameters uncertainties and some dynamics that are hard to model accurately, which causes certain challenges for designing model‐based high‐performance control algorithms. To solve these challenges, a parameter adaptive based neural network sliding mode control algorithm is proposed to enhance control performance of the electro‐hydraulic system. The parameter adaptive law is developed to estimate unknown parameters of the system, the neural network is applied for compensating unmodeled dynamics, and then the final control law is designed by sliding mode control method, and the stability demonstration of the closed‐loop system is given. In the simulations, the effectiveness of the designed parameter adaptive law is verified. Extensive comparison experiments are performed on a real rock drilling jumbo driven by proportional valves, the experimental results demonstrate that the developed control algorithm obviously improves the control precision of hydraulic cylinder of the rock drilling jumbo compared with the traditional sliding mode and PID control algorithm, thus the designed control algorithm can be expanded and applied for general hydraulic servo control mechanism.

Pathogenic role of super-enhancers as potential therapeutic targets in lung cancer.

Lung cancer is still one of the deadliest malignancies today, and most patients with advanced lung cancer pass away from disease progression that is uncontrollable by medications. Super-enhancers (SEs) are large clusters of enhancers in the genome's non-coding sequences that actively trigger transcription. Although SEs have just been identified over the past 10years, their intricate structure and crucial role in determining cell identity and promoting tumorigenesis and progression are increasingly coming to light. Here, we review the structural composition of SEs, the auto-regulatory circuits, the control mechanisms of downstream genes and pathways, and the characterization of subgroups classified according to SEs in lung cancer. Additionally, we discuss the therapeutic targets, several small-molecule inhibitors, and available treatment options for SEs in lung cancer. Combination therapies have demonstrated considerable advantages in preclinical models, and we anticipate that these drugs will soon enter clinical studies and benefit patients.

DeepSF-4mC: A deep learning model for predicting DNA cytosine 4mC methylation sites leveraging sequence features

N4-methylcytosine (4mC) is a DNA modification involving the addition of a methyl group to the fourth nitrogen atom of the cytosine base. This modification may influence gene regulation, providing potential insights into gene control mechanisms. Traditional laboratory methods for detecting 4mC DNA methylation have limitations, but the rise of artificial intelligence has introduced efficient computational strategies for 4mC site prediction. Despite this progress, challenges persist in terms of model performance and interpretability. To tackle these challenges, we propose DeepSF-4mC, a deep learning model specifically designed for predicting DNA cytosine 4mC methylation sites by leveraging sequence features. Our approach incorporates multiple encoding techniques to enhance prediction accuracy, increase model stability, and reduce the computational resources needed. Leveraging transfer learning, we harness existing models to enhance performance through learned representations or fine-tuning. Ensemble learning techniques combine predictions from multiple models, boosting robustness and accuracy. This research contributes to DNA methylation analysis and lays the groundwork for understanding 4mC's multifaceted role in biological processes. The web server for DeepSF-4mC is accessible at: http://deepsf-4mc.top/and the original code can be found at: https://github.com/754131799/DeepSF-4mC.

RNA polymerase II pausing is essential during spermatogenesis for appropriate gene expression and completion of meiosis

Male germ cell development requires precise regulation of gene activity in a cell-type and stage-specific manner, with perturbations in gene expression during spermatogenesis associated with infertility. Here, we use steady-state, nascent and single-cell RNA sequencing strategies to comprehensively characterize gene expression across male germ cell populations, to dissect the mechanisms of gene control and provide new insights towards therapy. We discover a requirement for pausing of RNA Polymerase II (Pol II) at the earliest stages of sperm differentiation to establish the landscape of gene activity across development. Accordingly, genetic knockout of the Pol II pause-inducing factor NELF in immature germ cells blocks differentiation to spermatids. Further, we uncover unanticipated roles for Pol II pausing in the regulation of meiosis during spermatogenesis, with the presence of paused Pol II associated with double-strand break (DSB) formation, and disruption of meiotic gene expression and DSB repair in germ cells lacking NELF.

Inheritance Pattern of A1 Cytoplasmic-nuclear Male Sterility System in Commercial Pearl Millet Hybrids [Pennisetum glaucum (L). R. Br.] in Summer and Post-rainy Seasons

Background: This study aimed to understand the genetic aspects and inheritance patterns that control the process of restoring fertility in the context of the A1 system of Cytoplasmic-Nuclear Male Sterility (CMS) in pearl millet. Methods: The experimentation was conducted in commercial pearl millet hybrids, utilizing three F2 populations and three BC1 populations. These populations underwent assessment during the rainy and post-rainy seasons at Rallis India Limited, Hyderabad During the Post-rainy (November-February) and summer (March-June) seasons of 2022-2023. Segregation data derived from observations on pollen shedding and seed set were gathered and subsequently, statistical analysis was performed. The Chi-square (χ2) test was employed to assess the conformity of the observed segregation data to the expected genetic ratios, thus evaluating the goodness of fit. Result: The hybrid combinations MP13P025A ×MP16P050R (MP7171) and MP18P069A × MP20P081R (MP7214) consistently displayed a 3:1 segregation ratio in the F2 generation and a 1:1 ratio in the BC1 generation, regardless of the rainy or post-rainy seasons. However, the cross between MP14030A and MP15P038R (MP7878) showed irregularities in both seasons due to modifiers and environmental factors. These irregularities stemmed from an excess of fertile plants (FF) in the post-rainy season or an excess of sterile plants (FS) in the summer season. These observations provide valuable insights into the genetic dynamics of the A1 Cytoplasmic-Nuclear Male Sterility (CMS) system within commercial pearl millet hybrids. The study indicates that fertility restoration in the A1-based CMS system is strongly influenced by a single Dominant gene control mechanism governing the interplay between male sterility and fertility restoration in these crosses.

Comparative transcriptome profile reveals insight into the antibacterial immunity mechanism of the loach (Misgurnus anguillicaudatus) fed with soybean fermented broth during lipopolysaccharide (LPS) exposure

Loach (Misgurnus anguillicaudatus) is a common freshwater commercial fish species in China. The meat of this fish is a good source of protein and other nutrients that are needed for human health. Aquaculture challenges such as diseases and pest susceptibility, excessive density, and nutritional deficiency result in low production of loach rather than increased demand. Due to a lack of knowledge about the immune system of loaches, we carried out this study to better understand its antibacterial molecular mechanism. Here, we performed RNA sequencing from liver tissue obtained from soya bean-fermented fed loach after subjecting it to the LPS challenge. The results revealed a total of 18,399 differentially expressed genes (DEGs) in the LPS-treated and control groups. There were 7482 DEGs that were upregulated and 10,917 DEGs were downregulated. The enrichment analysis of DEGs revealed that the majority of DEGs were found to be abundant in the pathways of DNA replication, spliceosome, nucleotide exception repair, cell cycle, and Herpes simplex virus 1 infection. Furthermore, qRT-PCR analysis of 21 selected DEGs demonstrated that the transcriptomic data is extremely reliable. Overall, this study provides insight into the molecular features and control mechanisms of genes that affect loach growth. The availability of this information will also contribute to the enhancement of the breeding and protection of loach resources.

Modulation of protein-DNA binding reveals mechanisms of spatiotemporal gene control in early Drosophila embryos.

It is well known that enhancers regulate the spatiotemporal expression of their target genes by recruiting transcription factors (TFs) to the cognate binding sites in the region. However, the role of multiple binding sites for the same TFs and their specific spatial arrangement in determining the overall competency of the enhancer has yet to be fully understood. In this study, we utilized the MS2-MCP live imaging technique to quantitatively analyze the regulatory logic of the snail distal enhancer in early Drosophila embryos. Through systematic modulation of Dorsal and Twist binding motifs in this enhancer, we found that a mutation in any one of these binding sites causes a drastic reduction in transcriptional amplitude, resulting in a reduction in mRNA production of the target gene. We provide evidence of synergy, such that multiple binding sites with moderate affinities cooperatively recruit more TFs to drive stronger transcriptional activity than a single site. Moreover, a Hidden Markov-based stochastic model of transcription reveals that embryos with mutated binding sites have a higher probability of returning to the inactive promoter state. We propose that TF-DNA binding regulates spatial and temporal gene expression and drives robust pattern formation by modulating transcriptional kinetics and tuning bursting rates.

Lack of Methylation Changes in GJB2 and RB1 Non-coding Regions of Cochlear Implant Patients with Sensorineural Hearing Loss.

Recent advances in epigenetic studies continue to reveal novel mechanisms of gene regulation and control, however little is known on the role of epigenetics in sensorineural hearing loss (SNHL) in humans. We aimed to investigate the methylation patterns of two regions, one in RB1 and another in GJB2 in Filipino patients with SNHL compared to hearing control individuals. We investigated an RB1 promoter region that was previously identified as differentially methylated in children with SNHL and lead exposure. Additionally, we investigated a sequence in an enhancer-like region within GJB2 that contains four CpGs in close proximity. Bisulfite conversion was performed on salivary DNA samples from 15 children with SNHL and 45 unrelated ethnically-matched individuals. We then performed methylation-specific real-time PCR analysis (qMSP) using TaqMan® probes to determine percentage methylation of the two regions. Using qMSP, both our cases and controls had zero methylation at the targeted GJB2 and RB1 regions. Our study showed no changes in methylation at the selected CpG regions in RB1 and GJB2 in the two comparison groups with or without SNHL. This may be due to a lack of environmental exposures to these target regions. Other epigenetic marks may be present around these regions as well as those of other HL-associated genes.

Hnf4 activates mimetic-cell enhancers to recapitulate gut and liver development within the thymus.

Mimetic cells are medullary thymic epithelial cells (mTECs) that mimic extra-thymic cell types to tolerize T cells to self-antigens. Here, we dissected the biology of entero-hepato mTECs, mimetic cells expressing gut- and liver-associated transcripts. Entero-hepato mTECs conserved their thymic identity yet accessed wide swaths of enterocyte chromatin and transcriptional programs via the transcription factors Hnf4α and Hnf4γ. Deletion of Hnf4α and Hnf4γ in TECs ablated entero-hepato mTECs and downregulated numerous gut- and liver-associated transcripts, with a primary contribution from Hnf4γ. Loss of Hnf4 impaired enhancer activation and CTCF redistribution in mTECs but did not impact Polycomb-mediated repression or promoter-proximal histone marks. By single-cell RNA sequencing, Hnf4 loss produced three distinct effects on mimetic cell state, fate, and accumulation. Serendipitously, a requirement for Hnf4 in microfold mTECs was discovered, which exposed a requirement for Hnf4γ in gut microfold cells and the IgA response. Study of Hnf4 in entero-hepato mTECs thus revealed mechanisms of gene control in the thymus and periphery alike.

Exploring the Effect of Late, Unbalanced Bilingualism on Cognitive Control

One of the most fascinating and enduring mysteries of human cognition concerns the process of cognitive control, a function that depends on the engagement of the prefrontal cortex (Miller, 2000) in order to coordinate thoughts and actions (Koechlin, Ody, & Kouneiher, 2003). Considering language switching as a practice to improve the general control mechanisms, the effect of bilingual experience on cognitive control has been a matter of scientific debate in the past two decades. The existence of bilingual advantage, however, has remained highly controversial in the bilingualism literature because of a mix of negative, positive, and null effects. The current study investigated the influence of late unbalanced bilingualism on cognitive control among 97 participants aged 18 to 40 years. A group of 63 Iranian monolinguals and 34 Persian-English bilinguals took part in this study and were exposed to a computerized version of Stroop Color and Word Task so as to measure conflict monitoring and inhibition. An independent samples t-test analysis of the Stroop results showed no significant differences in the mean color-word interference effects (RT and score) across both groups. Therefore, late unbalanced bilinguals are not cognitively different from their monolingual counterparts. The study findings indicate that the role of other key variables such as intellectual, physical, and social activities should further be considered in dealing with the notion of bilingualism and cognitive control.

Dynamics of alpha suppression index both modality specific and general attention processes

EEG alpha power varies under many circumstances requiring visual attention. However, mounting evidence indicates that alpha may not only serve visual processing, but also the processing of stimuli presented in other sensory modalities, including hearing. We previously showed that alpha dynamics during an auditory task vary as a function of competition from the visual modality (Clements et al., 2022) suggesting that alpha may be engaged in multimodal processing. Here we assessed the impact of allocating attention to the visual or auditory modality on alpha dynamics at parietal and occipital electrodes, during the preparatory period of a cued-conflict task. In this task, bimodal precues indicated the modality (vision, hearing) relevant to a subsequent reaction stimulus, allowing us to assess alpha during modality-specific preparation and while switching between modalities. Alpha suppression following the precue occurred in all conditions, indicating that it may reflect general preparatory mechanisms. However, we observed a switch effect when preparing to attend to the auditory modality, in which greater alpha suppression was elicited when switching to the auditory modality compared to repeating. No switch effect was evident when preparing to attend to visual information (although robust suppression did occur in both conditions). In addition, waning alpha suppression preceded error trials, irrespective of sensory modality. These findings indicate that alpha can be used to monitor the level of preparatory attention to process both visual and auditory information, and support the emerging view that alpha band activity may index a general attention control mechanism used across modalities.

Modelling ribosome kinetics and translational control on dynamic mRNA

The control of protein synthesis and the overall levels of various proteins in the cell is critical for achieving homoeostasis. Regulation of protein levels can occur at the transcriptional level, where the total number of messenger RNAs in the overall transcriptome are controlled, or at the translational level, where interactions of proteins and ribosomes with the messenger RNA determine protein translational efficiency. Although transcriptional control of mRNA levels is the most commonly used regulatory control mechanism in cells, positive-sense single-stranded RNA viruses often utilise translational control mechanisms to regulate their proteins in the host cell. Here I detail a computational method for stochastically simulating protein synthesis on a dynamic messenger RNA using the Gillespie algorithm, where the mRNA is allowed to co-translationally fold in response to ribosome movement. Applying the model to the test case of the bacteriophage MS2 virus, I show that the models ability to accurately reproduce experimental measurements of coat protein production and translational repression of the viral RNA dependant RNA polymerase at high coat protein concentrations. The computational techniques reported here open up the potential to examine the infection dynamics of a ssRNA virus in a host cell at the level of the genomic RNA, as well as examine general translation control mechanisms present in polycistronic mRNAs.

Differences in Immunohistochemical and Ultrastructural Features between Podocytes and Parietal Epithelial Cells (PECs) Are Observed in Developing, Healthy Postnatal, and Pathologically Changed Human Kidneys.

During human kidney development, cells of the proximal nephron gradually differentiate into podocytes and parietal epithelial cells (PECs). Podocytes are terminally differentiated cells that play a key role in both normal and pathological kidney function. Therefore, the potential of podocytes to regenerate or be replaced by other cell populations (PECs) is of great interest for the possible treatment of kidney diseases. In the present study, we analyzed the proliferation and differentiation capabilities of podocytes and PECs, changes in the expression pattern of nestin, and several early proteins including WNT4, Notch2, and Snail, as well as Ki-67, in tissues of developing, postnatal, and pathologically changed human kidneys by using immunohistochemistry and electron microscopy. Developing PECs showed a higher proliferation rate than podocytes, whereas nestin expression characterized only podocytes and pathologically changed kidneys. In the developing kidneys, WNT4 and Notch2 expression increased moderately in podocytes and strongly in PECs, whereas Snail increased only in PECs in the later fetal period. During human kidney development, WNT4, Notch2, and Snail are involved in early nephrogenesis control. In kidneys affected by congenital nephrotic syndrome of the Finnish type (CNF) and focal segmental glomerulosclerosis (FSGS), WNT4 decreased in both cell populations, whereas Notch2 decreased in FSGS. In contrast, Snail increased both in CNF and FSGS, whereas Notch2 increased only in CNF. Electron microscopy revealed cytoplasmic processes spanning the urinary space between the podocytes and PECs in developing and healthy postnatal kidneys, whereas the CNF and FSGS kidneys were characterized by numerous cellular bridges containing cells with strong expression of nestin and all analyzed proteins. Our results indicate that the mechanisms of gene control in nephrogenesis are reactivated under pathological conditions. These mechanisms could have a role in restoring glomerular integrity by potentially inducing the regeneration of podocytes from PECs.

Interferons reshape the 3D conformation and accessibility of macrophage chromatin

SummaryEngagement of macrophages in innate immune responses is directed by type I and type II interferons (IFN-I and IFN-γ, respectively). IFN triggers drastic changes in cellular transcriptomes, executed by JAK-STAT signal transduction and the transcriptional control of interferon-stimulated genes (ISG) by STAT transcription factors. Here, we study the immediate-early nuclear response to IFN-I and IFN-γ in murine macrophages. We show that the mechanism of gene control by both cytokines includes a rapid increase of DNA accessibility and rearrangement of the 3D chromatin contacts particularly between open chromatin of ISG loci. IFN-stimulated gene factor 3 (ISGF3), the major transcriptional regulator of ISG, controlled homeostatic and, most notably, induced-state DNA accessibility at a subset of ISG. Increases in DNA accessibility correlated with the appearance of activating histone marks at surrounding nucleosomes. Collectively our data emphasize changes in the three-dimensional nuclear space and epigenome as an important facet of transcriptional control by the IFN-induced JAK-STAT pathway.

Interference of novobiocin in the expression of a truncated blaCTX-M gene causes a phenotypic variation in the production of β-lactamases in Escherichia coli strain EC1091

BackgroundThe environment of a previous novel blaCTX-M gene is investigated in the current study. Sequencing the boundaries of the gene revealed the presence of a mosaic genetic element containing a misc. feature (referring to the novel blaCTX-M). The sequence of the mosaic element is deposited to GenBank (accession no. MT215579). MethodsReverse transcription PCR and production of β-lactamases by nitrocefin colorimetric β-lactamase activity assay were used to evaluate the expression and production of β-lactamases in the Escherichia coli strain EC1091. ResultsWhen investigating the β-lactamase production in EC1091, the truncated gene showed variable enzyme productions. The production was only maintained under sub-inhibitory concentrations of novobiocin. The production of β-lactamases reported a (1.2–2.2) fold increase compared to basal treatments. The obtained results document for the first time the interference of a coumarin antibiotic in the expression of β-lactamases suggesting a control mechanism for the truncated blaCTX-M gene. High similarities were found by BLASTN search between the sequence of the mosaic element to certain determinants in pC15.1a and AR_0015 plasmids. ConclusionFurther investigation of the truncated gene or its homologs in other genomes may provide valuable data in terms of the evolution, resistance, and control mechanisms of bla genes.

From rejection to symbiosis. Human-infectious agents relations : a general theory of physiology and pathology. The contribution of tropical medicine.

In this paper, the word symbiosis (from the Greek Sumbiōsis) is used in its original sense and refers to all organisms which interact with each other, whether this association is beneficial, neutral or harmful to the host (mutualism, commensalism and parasitism). Symbiosis is found in every aspect of the living world. It is seen between infectious agents, in tropical disease vectors, in the human body and in illnesses. Immune-dependent symbiosis between infectious agents and the host is an opposite and complementary mechanism to defense and rejection immunity. This duality is found in many biological functions. Our comprehensive, compelling theory provides an overview of the different sites and mechanisms where symbiosis may occur. These symbioses are ongoing, fourdimensional evolutionary processes. They are gradually shifting away from phenotypic symbioses, including exosymbioses (metazoans, protozoa, yeasts, bacteria, viruses), tissular endosymbioses (metazoans, yeast), toward cytoplasmic and nuclear endosymbioses (protozoa, yeasts, bacteria, RNA viruses), before finally arriving at genomic endosymbioses (mitochondrial DNA, DNA viruses, retroviruses, transposable elements), which is the ultimate goal of symbiotic evolution, giving rise to new human genes. The phenotype/genotype boundary is thus traversable. A immunological process that initially takes an immunopathologic inflammatory form, but develops into a non-inflammatory immuno-physiological state. A process that leads from parasitism to mutualism and commensalism, and ultimately to the emergence of new species. This article hinges on the primary author’s extensive experience in tropical medicine allied with meticulous bibliographic research. Our intention is to offer a fresh perspective on the different forms of physiological and pathological symbioses in humans and illustrate them with examples. The general control mechanisms of symbiosis are discussed including immune tolerance and rejection. Innate immunity requires an assumption about the evolutionary mechanisms involved in recognition of immune innate material. In adaptive immunity we develop the hypothetical role of antibody dependent cell tolerance (ADCT) in which cytophilic antibodies support immune-dependent symbiosis. This includes then the crucial role of growth and differentiation factors in symbiotic mechanisms. We will list ten areas of research and application in fundamental science (self-genomics, immune innate material), epidemiology, prevention (nuclear endomembrane, symbiogenic vaccination) and treatment (including differentiation therapy), which bring together internists, infectious disease specialists, oncologists, biologists, immunologists, geneticists, epidemiologists, nutritionists, botanists and evolutionary scientists.

Cancer Genetics and Epigenetics in Cancer Risk Assesment

Compared to the normal tissues, cancer cells tend to have higher proliferation rate and often lost their ability to undergo apoptosis. In addition, cancer cells can separate themselves from their original tissue thus causing metastasis in other part of body. While undergoing program cell death, disordered cellular programming can happen. The main causes of this cellular programming anomaly are epigenetic and genetic alterations, which have been known as two separate mechanisms in carcinogenetic. A recent outcome of whole exome sequencing of thousands of human cancers has been the unexpected discovery of many inactivating mutations in genes that control the epigenome. These mutations have the potential to disturb the DNA methylation patterns, histone modifications, and nucleosome positioning, hence, the causing gene expression alternation. Genetic alteration of the epigenome therefore contributes to cancer just as epigenetic process can cause point mutations and disable DNA repair functions. Epigenetic mechanisms changes could cause genetic mutations, and genetic mutations in epigenetic regulators could cause epigenome changes. Knowing that epigenome play a major role in the hierarchy of gene control mechanisms suggests that mutations might have impact on multiple pathways related to cancer phenotype. This pinpoint the fact that recently, the way the genes are organized and controlled are suggested to be a relevant factor for human carcinogenesis.Keywords: cancer genetic, cancer epigenetic, oncogens, tumor suppressor genes, driver mutation, passenger mutation

Primordial super-enhancers: heat shock-induced chromatin organization in yeast.

Specialized mechanisms ensure proper expression of critically important genes such as those specifying cell identity or conferring protection from environmental stress. Investigations of the heat shock response have been critical in elucidating basic concepts of transcriptional control. Recent studies demonstrate that in response to thermal stress, heat shock-responsive genes associate with high levels of transcriptional activators and coactivators and those in yeast intensely interact across and between chromosomes, coalescing into condensates. In mammalian cells, cell identity genes that are regulated by super-enhancers (SEs) are also densely occupied by transcriptional machinery that form phase-separated condensates. We suggest that the stress-remodeled yeast nucleome bears functional and structural resemblance to mammalian SEs, and will reveal fundamental mechanisms of gene control by transcriptional condensates.

Histone Recognition by the BDP1 Bromodomain of Plasmodium falciparum

Bromodomains are evolutionarily conserved protein modules that specifically recognize acetylated lysine residues on histone tails of the nucleosome. During the red-blood-cell-stage of infection with Plasmodium falciparum, the parasite undergoes repeated rounds of replication, egress, and invasion. Erythrocyte invasion involves specific interactions between host cell receptors and parasite ligands and coordinated expression of genes specific to this step of the life cycle. A parasite-specific protein known as bromodomain protein 1 (PfBDP1) binds to chromatin at the transcriptional start sites of invasion-related genes and directly controls their expression. Conditional PfBDP1 knockdown causes a dramatic defect in parasite invasion and growth, and results in transcriptional down-regulation of multiple invasion-related genes at a time point critical for invasion. Conversely, PfBDP1 overexpression enhances expression of these same invasion-related genes. PfBDP1 has been shown to interact with acetylated histone H3 and a second bromodomain protein, PfBDP2, suggesting a potential mechanism for gene recognition and control. Since PfBDP1 critically coordinates expression of invasion genes, targeting PfBDP1 could be an invaluable tool in mitigating malaria infections. The domain architecture of PfBDP1 includes a single C-terminal bromodomain and several ankyrin repeats. PfBDP1 is thought to act by tethering a transcriptional activator complex to acetylated histone H3 to control genes required for parasite invasion. We hypothesized that the bromodomain is crucial for this function of PfBDP1 via recognition of acetylated lysine modifications. We carried out several histone binding assays to identify novel histone interactions the of PfBDP1 bromodomain. We also utilized a combination of structural biology and biophysical approaches to identify amino acid residues critical for ligand coordination. The result of this study will provide molecular details about the recognition of acetylated histone ligands by the PfBDP1 bromodomain and shed light on how this domain recruits the PfBDP1-PfBDP2 complex to chromatin. Importantly, these results may improve the development of new therapeutics to treat malaria