RESUMO
Transcription factor (TF)-cofactor (COF) interactions define dynamic, cell-specific networks that govern gene expression; however, these networks are understudied due to a lack of methods for high-throughput profiling of DNA-bound TF-COF complexes. Here we describe the Cofactor Recruitment (CoRec) method for rapid profiling of cell-specific TF-COF complexes. We define a lysine acetyltransferase (KAT)-TF network in resting and stimulated T cells. We find promiscuous recruitment of KATs for many TFs and that 35% of KAT-TF interactions are condition specific. KAT-TF interactions identify NF-κB as a primary regulator of acutely induced H3K27ac. Finally, we find that heterotypic clustering of CBP/P300-recruiting TFs is a strong predictor of total promoter H3K27ac. Our data supports clustering of TF sites that broadly recruit KATs as a mechanism for widespread co-occurring histone acetylation marks. CoRec can be readily applied to different cell systems and provides a powerful approach to define TF-COF networks impacting chromatin state and gene regulation.
RESUMO
BACKGROUND & OBJECTIVE: Since the first report of HIV-1 infection in Tamil Nadu, India, HIV-1 seroprevalence in India has increased steadily. Though interventions to prevent mother-to-child transmission (MTCT) are available, their implementation is a significant challenge. Therefore, among pregnant women in rural Tamil Nadu, the acceptance of education regarding HIV-1 infection and transmission and, among a systematic sample, knowledge, attitudes, and beliefs; the acceptance of HIV-1 voluntary counselling and testing (VCT); and the seroprevalence of HIV-1 infection as well as risk factors for seropositivity were assessed. METHODS: Pregnant women registered in the antenatal clinics at Namakkal District Hospital and Rasipuram Government Hospital, Tamil Nadu, India, were offered an educational session regarding HIV-1 infection and transmission. HIV-1 VCT, with informed consent, was offered. Positive results with HIV-1 rapid testing were confirmed with HIV-1 ELISA and Western blot assays. With informed consent, a systematic sample of the study population was asked to participate in pre- and posteducation assessments. Chi-square tests were used to evaluate HIV-1 risk factors. RESULTS: The educational session as well as VCT were well accepted by rural, pregnant, HIV-1- infected women. Of 3722 women registered for antenatal care at the two hospitals over a one year period, 3691 (99.2%) agreed to participate in the educational session and 3715 (99.8%) had VCT [74 had confirmed HIV-1 infection [seroprevalence: 2.0% (95% confidence interval (95%CI): 1.6%, 2.5%)]]. Of 759 eligible women, a systematic sample of 757 (99.7%) women participated in the pre- and post-education assessments. Although baseline knowledge regarding HIV-1 was limited, a highly significant improvement in such knowledge was observed (P<0.0001 for all comparisons of changes in knowledge, attitudes, and beliefs measured before and immediately after the educational session). The median per cent of correct responses increased from 26.4 per cent before the educational session to 93.8 per cent afterwards. Women whose husbands were long distance truck drivers were at increased risk of HIV-1 infection. Other factors associated with HIV-1 infection were clinical site (Namakkal District Hospital), a smaller number of persons in the household, being unmarried, and a history of previous surgeries. INTERPRETATION & CONCLUSION: The acceptability of education and of VCT among antenatal clinic attendees in this study was encouraging. However, the relatively high seroprevalence highlights the spread of HIV-1 from high risk groups to the general population and emphasizes the need for primary prevention of HIV-1 infection among adolescent girls and women of reproductive age in India.
