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Mus musculus

ABSTRACT: Deciphering the importance of the palindromic architecture of the immunoglobulin heavy chain 3’ regulatory region.

PROVIDER: PRJNA307097 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3057276_1.fastq.gz	Fastqsanger.gz
	SRR3057276_2.fastq.gz	Fastqsanger.gz
	SRR3057277_1.fastq.gz	Fastqsanger.gz
	SRR3057277_2.fastq.gz	Fastqsanger.gz
	SRR3057278_1.fastq.gz	Fastqsanger.gz

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Mus musculus

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Deciphering the importance of the palindromic architecture of the immunoglobulin heavy chain 3â?? regulatory region.

Project description:The IgH 3â?? regulatory region (3â??RR) controls class switch recombination (CSR) and somatic hypermutation (SHM) in B cells. The mouse 3â??RR contains four enhancer elements with hs1,2 flanked by inverted repeated sequences and the center of a 25-kb palindrome bounded by two hs3 enhancer inverted copies (hs3a and hs3b). hs4 lies downstream of the palindrome. Evolution maintained in mammals this unique palindromic arrangement suggesting that it is functionally significant. We report that deconstructing the palindromic IgH 3â??RR strongly impacts its function even when enhancers are preserved. CSR and IgH transcription appear poorly dependent from the 3â??RR architecture and are more or less preserved provided 3â??RR enhancers are present. By contrast, an â??architectural effectâ?? significantly lowers VH germline transcription, AID recruitment and SHM. In conclusion, this work indicates that the IgH 3â??RR does not simply pile up enhancer units but also optimally expose them into a functional architecture of crucial importance. RNAseq analysis of B-cell splenocytes with (S=stimulated) or without (R=resting) LPS activation from wt, delta2leftPAL, and deltaIRIS mice.

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Project description:Paddy rice with husk can be availbale for chicken dietary resource instead of yellow corn. Ingestion of paddy rice potentially affects on gastrointestinal physiology and function including digestion/absorption of nutrients and gut barrier function such as mucosal immunity, but the details of changes is unknown. To obtain insight into the physiological modifications in the small intestine of chickens fed paddy rice, we conducted a comprehensive analysis of gene expression in small intestine by DNA microarray. In the paddy rice group, a total of 120 genes were elevated >1.5-fold in the paddy rice group, whereas a total of 159 genes were diminished < 1.5-fold. Remarkably, the gene expression levels of IGHA (immunoglobulin heavy chain α), IGJ (immunoglobulin J chain), and IGLL1 (immunoglobulin light chain λ chain region), which constitute immunoglobulin A, decreased 3 to 10 times in the paddy rice group.

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mutated IGHV3-23 CLL

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Multiway chromatin conformation analyses at the human immunoglobulin heavy chain locus reveal regulatory principles underlying somatic hypermutation [ChIP-Seq]

Project description:The generation of protective antibodies by somatic hypermutation (SHM) is essential for antibody maturation and adaptive immunity. SHM involves co-transcriptional mutagenesis of immunoglobulin variable (V) regions regulated by enhancers located hundreds of kilobases away. How 3D chromatin structure affects SHM is poorly understood. Here, we measure higher-order interactions on single alleles of the human immunoglobulin heavy chain locus (IGH) using Tri-C. We find that SHM is underpinned by a multiway hub wherein the V region is proximal to all enhancers. Cohesin-mediated loop extrusion is dispensable for IGH transcription and hub architecture. Transcription and mutagenesis of IGH switch regions, which are necessary for antibody class-switch recombination, creates new chromatin loops that can form without cohesin. However, these additional loops do not compromise hub integrity, V region transcription or SHM. Thus, antibody maturation occurs within a multiway hub accommodating several gene-enhancer loops wherein transcription and mutagenesis of different segments can occur non-competitively.

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