Unknown,Transcriptomics,Genomics,Proteomics

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Comparative profiling of chromatin state maps and transcription factor occupancy during human fetal and adult erythropoiesis


ABSTRACT: We report the comparative investigation of genome-wide chromatin state maps, transcription factor (TF) occupancy, and gene expression profiles from developing red cell precursors at two developmental stages. Contrasting the similarities and differences between fetal and adult erythropoiesis provides important insights into the erythroid gene expression programs and gene regulatory networks. Specifically, comparative analyses of human erythropoiesis identify developmental stage-specific enhancers as primary determinants of stage-specific gene expression programs. We find that master regulators, such as GATA1 and TAL1, cooperatively act within active enhancers but have little predictive value for stage-specific enhancer activity. Instead, a set of stage-specific co-regulators collaborates with master regulators and contributes to differential gene expression. We further identify and validate IRF2, IRF6, and MYB as effectors of adult-stage expression program. Thus, the combinatorial assembly of master regulators and transcriptional co-regulators at developmental stage-specific enhancers controls gene expression programs and temporal regulation of transcriptional networks in a mammalian genome. Examination of various histone modifications and transcription factor occupancy by ChIP-seq in fetal and adult proerythroblasts.

ORGANISM(S): Homo sapiens

SUBMITTER: Jian Xu 

PROVIDER: E-GEOD-36985 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Combinatorial assembly of developmental stage-specific enhancers controls gene expression programs during human erythropoiesis.

Xu Jian J   Shao Zhen Z   Glass Kimberly K   Bauer Daniel E DE   Pinello Luca L   Van Handel Ben B   Hou Serena S   Stamatoyannopoulos John A JA   Mikkola Hanna K A HK   Yuan Guo-Cheng GC   Orkin Stuart H SH  

Developmental cell 20121004 4


Gene-distal enhancers are critical for tissue-specific gene expression, but their genomic determinants within a specific lineage at different stages of development are unknown. Here we profile chromatin state maps, transcription factor occupancy, and gene expression profiles during human erythroid development at fetal and adult stages. Comparative analyses of human erythropoiesis identify developmental stage-specific enhancers as primary determinants of stage-specific gene expression programs. W  ...[more]

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