H3 Lysine 4 Is Acetylated at Active Gene Promoters and Is Regulated by H3 Lysine 4 Methylation

Methylation of histone H3 lysine 4 (H3K4me) is an evolutionarily conserved modification whose role in the regulation of gene expression has been extensively studied. In contrast, the function of H3K4 acetylation (H3K4ac) has received little attention because of a lack of tools to separate its function from that of H3K4me. Here we show that, in addition to being methylated, H3K4 is also acetylated in budding yeast. Genetic studies reveal that the histone acetyltransferases (HATs) Gcn5 and Rtt109 contribute to H3K4 acetylation in vivo. Whilst removal of H3K4ac from euchromatin mainly requires the histone deacetylase (HDAC) Hst1, Sir2 is needed for H3K4 deacetylation in heterochomatin. Using genome-wide chromatin immunoprecipitation (ChIP), we show that H3K4ac is enriched at promoters of actively transcribed genes and located just upstream of H3K4 tri-methylation (H3K4me3), a pattern that has been conserved in human cells. We find that the Set1-containing complex (COMPASS), which promotes H3K4me2 and -me3, also serves to limit the abundance of H3K4ac at gene promoters. In addition, we identify a group of genes that have high levels of H3K4ac in their promoters and are inadequately expressed in H3-K4R, but not in set1Δ mutant strains, suggesting that H3K4ac plays a positive role in transcription. Our results reveal a novel regulatory feature of promoter-proximal chromatin, involving mutually exclusive histone modifications of the same histone residue (H3K4ac and H3K4me)

MÉTODOS DE INDEXAÇÃO DE INDICADORES NA AVALIAÇÃO DA QUALIDADE DO SOLO EM RELAÇÃO À EROSÃO HÍDRICA

A avaliação da qualidade dos solos agrícolas é importante para definição e adoção de práticas de manejo que garantam a sustentabilidade socioeconômica e ambiental. Os métodos de indexação dos indicadores de qualidade denominados Índice de Qualidade Integrado (IQI) e Índice de Qualidade Nemoro (IQN) foram utilizados neste estudo para avaliar a qualidade de solo em áreas experimentais de plantio de eucalipto. A seleção dos indicadores foi feita a partir de nove indicadores de qualidade do solo: diâmetro médio geométrico, permeabilidade à água, matéria orgânica, macro e microporosidade, volume total de poros, densidade do solo, resistência à penetração e índice de floculação, que estão relacionados à erosão hídrica. Os tratamentos constituíram de eucalipto plantado em nível, com e sem a manutenção dos resíduos, em desnível e solo descoberto, em dois biomas distintos, cujas vegetações nativas são Cerrado e Floresta. Os índices de qualidade do solo (IQS) apresentaram alta correlação com a erosão hídrica. Entre os sistemas manejados, o Eucalipto com manutenção do resíduo evidenciou valores mais elevados em ambos os índices, ressaltando-se a importância da cobertura vegetal e manutenção da matéria orgânica para conservação do solo e da água em sistemas florestais. Os IQS demonstraram alto coeficiente de correlação inversa com as perdas de solo e água. Em locais com as maiores taxas de erosão hídrica manifestaram também os menores valores de IQI e IQN. Assim, os índices testados permitiram avaliar com eficácia os efeitos dos manejos adotados sobre a qualidade do solo em relação à erosão hídrica

Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium

BACKGROUND Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC. METHODS Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals). RESULTS Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation. CONCLUSION This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts