This study investigates the combinatorial patterns of histone acetylations and methylations in the human genome, focusing on CD4+ T cells. The researchers analyzed 39 histone modifications and identified a common modification module consisting of 17 modifications detected at 3,286 promoters. These modifications tend to colocalize in the genome and correlate with each other at the individual nucleosome level. Genes associated with this module tend to have higher expression, and the addition of more modifications is associated with further increased expression. The study suggests that these histone modifications may act cooperatively to prepare chromatin for transcriptional activation. Histone modifications, including acetylation and methylation, play a crucial role in gene transcription. Acetylation is primarily associated with gene activation, while methylation can be associated with either repression or activation depending on its position and state. The study used ChIP-Seq to generate genome-wide maps of 18 histone acetylations and 19 histone methylations, and analyzed these together with previously generated H2A.Z and 19 histone methylation maps. The researchers found that all acetylation modifications positively correlated with gene expression, consistent with their involvement in transcriptional activation. However, different acetylation modifications targeted different regions of genes. For example, H2AK9ac, H2BK5ac, H3K9ac, H3K18ac, H3K27ac, H3K36ac, and H4K91ac were mainly located in the region surrounding the TSS, whereas H2BK12ac, H2BK20ac, H2BK120ac, H3K4ac, H4K5ac, H4K8ac, H4K12ac, and H4K16ac were elevated in the promoter and transcribed regions of active genes. The study identified 13 most prevalent modification patterns, each associated with more than 62 genes. These patterns were classified into three classes based on gene expression levels. Class I patterns were associated with low expression and contained H3K27me3, while Class II patterns were associated with intermediate expression and contained H3K36me3 or a modification backbone. Class III patterns were associated with high expression and included H2BK5me1, H4K16ac, H4K20me1, and H3K79me1/2/3. The study also examined the distribution of histone modifications at different functional regions, including promoters, enhancers, and gene bodies. The results showed that histone modifications are distributed differently across these regions, with some modifications being more prevalent in specific regions. The study found that the modification backbone, consisting of 17 modifications, was robust against perturbations and was associated with higher gene expression. The study also identified distinctThis study investigates the combinatorial patterns of histone acetylations and methylations in the human genome, focusing on CD4+ T cells. The researchers analyzed 39 histone modifications and identified a common modification module consisting of 17 modifications detected at 3,286 promoters. These modifications tend to colocalize in the genome and correlate with each other at the individual nucleosome level. Genes associated with this module tend to have higher expression, and the addition of more modifications is associated with further increased expression. The study suggests that these histone modifications may act cooperatively to prepare chromatin for transcriptional activation. Histone modifications, including acetylation and methylation, play a crucial role in gene transcription. Acetylation is primarily associated with gene activation, while methylation can be associated with either repression or activation depending on its position and state. The study used ChIP-Seq to generate genome-wide maps of 18 histone acetylations and 19 histone methylations, and analyzed these together with previously generated H2A.Z and 19 histone methylation maps. The researchers found that all acetylation modifications positively correlated with gene expression, consistent with their involvement in transcriptional activation. However, different acetylation modifications targeted different regions of genes. For example, H2AK9ac, H2BK5ac, H3K9ac, H3K18ac, H3K27ac, H3K36ac, and H4K91ac were mainly located in the region surrounding the TSS, whereas H2BK12ac, H2BK20ac, H2BK120ac, H3K4ac, H4K5ac, H4K8ac, H4K12ac, and H4K16ac were elevated in the promoter and transcribed regions of active genes. The study identified 13 most prevalent modification patterns, each associated with more than 62 genes. These patterns were classified into three classes based on gene expression levels. Class I patterns were associated with low expression and contained H3K27me3, while Class II patterns were associated with intermediate expression and contained H3K36me3 or a modification backbone. Class III patterns were associated with high expression and included H2BK5me1, H4K16ac, H4K20me1, and H3K79me1/2/3. The study also examined the distribution of histone modifications at different functional regions, including promoters, enhancers, and gene bodies. The results showed that histone modifications are distributed differently across these regions, with some modifications being more prevalent in specific regions. The study found that the modification backbone, consisting of 17 modifications, was robust against perturbations and was associated with higher gene expression. The study also identified distinct